БЕЛКИ, СВЯЗЫВАЮЩИЕ ВСМА, NKG2D И CD16

Изобретение относится к биохимии и медицине, в частности к полиспецифическим связывающим белкам, которые связываются с BCMA, рецептором NKG2D и CD16, а также фармацевтическим композициям и терапевтическим способам, полезным для лечения рака. Настоящее изобретение обеспечивает определенные преимущества для улучшения лечения рака, экспрессирующего ВСМА. 5 н. и 22 з.п. ф-лы, 39 ил., 8 табл., 11 пр.

ХИМЕРНЫЕ АНТИГЕННЫЕ РЕЦЕПТОРЫ, НАЦЕЛЕННЫЕ НА ПОДОБНЫЙ FC-РЕЦЕПТОРУ БЕЛОК 5, И ИХ ПРИМЕНЕНИЕ

Изобретение относится к области биотехнологии, в частности к химерному антигенному рецептору (CAR), который связывается с подобным Fc-рецептору белком 5 (FcRL5), а также к содержащим его композиции и набору. Также раскрыта молекула нуклеиновой кислоты, кодирующая вышеуказанный CAR, а также содержащие ее клетка и вектор. Изобретение эффективно для лечения опухоли, экспрессирующей FcRL5. 16 н. и 76 з.п. ф-лы, 27 ил., 240 табл., 10 пр.

ТЕРАПЕВТИЧЕСКИЕ СЛИТЫЕ БЕЛКИ

Настоящее изобретение относится к области биотехнологии, конкретно к рекомбинантному получению терапевтических слитых белков, усиливающих эффероцитоз, и может быть использовано в медицине в лечении или предупреждении воспалительного нарушения или воспалительного поражения органов, связанного со сниженным эффероцитозом. Предложены варианты слитых белков на основе интегрин-связывающего домена, фосфатидилсерин (PS)-связывающего домена и солюбилизирующего домена, в которых солюбилизирующий домен вставлен между интегрин-связывающим доменом и PS-связывающим доменом. Изобретение обеспечивает получение слитых белков на основе структуры встречающихся в природе мостиковых белков, а именно MFG-E8, которые функционируют с обеспечением связывания PS-представляющих погибающих клеток, дебриса и микрочастиц с фагоцитами и, таким образом, обеспечивают запуск эффероцитоза, при этом характеризуются сниженной липкостью и улучшенной растворимостью, более длительным временем воздействия в плазме крови и более ...

НОВАЯ ВАКЦИНА, НАПРАВЛЕННАЯ ПРОТИВ СОСУДОВ ОПУХОЛЕЙ, В КАЧЕСТВЕ ЭФФЕКТИВНОГО СРЕДСТВА В ТЕРАПИИ ОПУХОЛЕЙ

... 1. Вакцина, состоящая из одной аминокислотной последовательности экстра-домена В фибронектина (EDB), экстра-домена А фибронектина (EDA), аннексина А1, эндосиалина, экстра-домена С тенасцина С или белка «magic roundabout» (MR) либо по меньшей мере одного их фрагмента в его первоначальной или мультимерной форме, или состоящая из комбинации таких аминокислотных последовательностей или по меньшей мере одного такого фрагмента, присоединенной к молекуле-носителю, и фармацевтически приемлемого адъюванта.2. Вакцина по п.1, где EDB, EDA, аннексии А1, эндосиалин, экстра-домен С тенасцина С и белок «magic roundabout» (MR) имеют происхождение от человека, собаки, кошки или лошади.3. Вакцина, содержащая EDB, EDA, аннексии А1, эндосиалин, экстрадомен С тенасцина С и белок «magic roundabout» (MR), по п.1 или 2 для применения в медицине.4. Применение слитого белка, состоящего из полноразмерных EDB, EDA, аннексина А1, эндосиалина, экстра-домена С тенасцина С или белка «magic roundabout» (MR), имеющих происхождение ...

СПОСОБ ПОВЫШЕНИЯ ЧАСТОТЫ ИМПЛАНТАЦИИ ЭМБРИОНА В МАТЕРИНСКОЙ МАТКЕ МЛЕКОПИТАЮЩИХ, ПРИМЕНЕНИЕ ЭФФЕКТИВНОГО КОЛИЧЕСТВА БЕТА-ГАЛАКТОЗИД-СВЯЗЫВАЮЩЕГО ЛЕКТИНА ИЛИ ЕГО ПРОИЗВОДНЫХ, БЕТА-ГАЛАКТОЗИД-СВЯЗЫВАЮЩИЙ ЛЕКТИН ИЛИ ПРОИЗВОДНЫЕ И ПРОДУКТ

... 1. Способ повышения частоты имплантации эмбриона в матке здоровых млекопитающих, отличающийся тем, что он включает введение в матку млекопитающего эффективного количества бета-галактозид-связывающего лектина или его производных перед предимплантационным периодом.2. Способ по п.1, отличающийся тем, что количество, варьируемое от 0,0000001 до 1,0 мг активной формы бета-галактозид-связывающего лектина или его производного, вводят на килограмм веса тела млекопитающего.3. Способ по п.2, отличающийся тем, что активная форма бета-галактозид-связывающего лектина или производного находится в форме стерильного, стабильного, свободного от эндотоксина, изотонического носителя и имеет рН между 6,8 и 7,4.4. Способ по п.3, отличающийся тем, что носитель представляет собой буферированный раствор.5. Способ по п.4, отличающийся тем, что буферированный раствор выбирают из солевого фосфатного буфера (PBS) или физиологической сыворотки.6. Способ по п.1, отличающийся тем, что бета-галактозид-связывающий лектин ...

C-TYPE-LEKTIN-TRANSMEMBRAN-ANTIGEN, WHICH ARE EXPRIMIERT IN HUMAN ONE PROSTATAKREBS, AND USES OF THIS ANTIGEN

SOLUBLE HETERODIMERE RECEPTORS AND YOUR USE

Activating chimeric receptors and uses thereof in natural killer cell immunotherapy

Current invention relates to a polynucleotide encoding activating chimeric receptors comprising engineered Natural Killer Group 2 member C (NKG2C) having enhanced affinity for HLA class I histocompatibility antigen alpha chain E (HLA-E)/peptide complex or an extracellular receptor domain of NKG2A coupled to an effector domain. It also relates to NK cells expressing such constructs and the use of these NK cells to induce cytotoxicity. It further exemplifies that the NK cells expressing polynucleotide encoding NKG2C (SIIS)/CD94/DAP12 or NKG2C/CD94/4-1 BB/CD3z showed enhanced NK cytotoxicity against cancer cells.

NK cell-directed chimeric proteins

The present invention relates, inter alia, to compositions and methods, including chimeric proteins comprising an extracellular domain of a Type I transmembrane protein or a portion of a membrane-anchored extracellular protein and a portion of the extracellular domain of a Type II transmembrane protein, wherein the Type II transmembrane protein is naturally expressed on the surface of a Natural Killer (NK) cell that find use in the treatment of disease, such as cancer and viral infections.

Multispecific chimeric receptors comprising NKG2D domain and methods of use thereof

Provided are chimeric receptors targeting NKG2D, and multispecific chimeric receptors comprising an NKG2D domain and a second antigen binding domain such as an IL-3 domain. Also provided are dual chimeric receptor systems comprising a first chimeric receptor comprising an NKG2D domain, and a second chimeric receptor comprising a second antigen binding domain such as an IL-3 domain. Further provided are engineered immune effector cells (such as T cells), pharmaceutical compositions, kits and methods of treating cancer.

Porcine reproductive and respiratory syndrome virus resistant animals

The disclosure relates to genetically modified swine wherein at least one allele of a SIGLEC1 gene has been inactivated and/or at least one allele of a CD163 gene has been inactivated. Genetically modified swine having both alleles of the SIGLEC1 gene and/or both alleles CD 163 gene inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSV). Methods for producing such transgenic swine are also provided.

Method for modulating the binding activity of a novel ICAM-3 binding receptor on sinusoidal endothelial cells in liver and lymph nodes

C-type lectin transmembrane antigen expressed in human prostate cancer and uses thereof

Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy

The present invention provides compositions and methods for regulating the specificity and activity of immune effector cells for use in immunotherapy. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a "NKR-CAR" which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

Chimeric antigen receptors targeting Fc Receptor-like 5 and uses thereof

The presently disclosed subject matter provides for methods and compositions for treating a neoplasia ( ...

Soluble ligands for CD40

Chimeric antigen and T cell receptors and methods of use

The invention provides a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising extracellular domain disclosed herein. Some aspects of the invention relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising the extracellular domain disclosed herein. Other aspects of the invention relate to cells comprising the CAR or the TCR and their use in a T cell therapy.

Soluble interleukin-20 receptor

SOLUBLE RECOMBINANT FCE-RECEPTOR, THE PREPARATION AND THE USE THEREOF

Method for modulating the binding activity of a novel icam-3 binding receptor onsinusoidal endothelial cells in liver and lymph nodes

DNA MOLECULES ENCODING HUMAN CLAX PROTEINS AND THEIR SOLUBLE FUSION PROTEINS

Isolated novel cDNA sequences encoding a human C-type lectin and three homologues are provided. They are referred to herein as "CLAX" (C-type Lectin, Activation Expressed) proteins. The invention also includes methods of using the nucleic acid sequences, polypeptides encoded by the nucleic acid sequences disclosed herein, fusion proteins having all or a portion (e.g., an extracellular region) of the CLAX proteins, antibodies specific for the novel CLAXs, ligands and inhibitors for the novel CLAXs. The genes of CLAX are specifically expressed in lymphoid tissues and activated T lymphocytes but not resting T lymphocytes. The invention concers the utility in pharmaceutical compositions for the prevention and treatment of infectious, inflammatory and allergic diseases.

IL-31 IMPROVES EFFICACY OF MACROPHAGE-BASED ADOPTIVE CELL THERAPY FOR CANCER

The present invention provides macrophages genetically modified to express IL-31 or both IL- 31 and a chimeric antigen receptor (CAR) for treatment of cancer. It further provides methods for treatment of cancer comprising administration of IL-31 along with genetically unmodified macrophages or genetically modified to express a CAR.

MODIFIED NON-NATURAL NKG2D LIGANDS THAT SELECTIVELY DELIVER ATTACHED HETEROLOGOUS MOLECULES TO NON-NATURAL NKG2D RECEPTORS ON CAR-CELLS

This application relates generally to the production of modified, non-natural a1-a2 domains of NKG2D ligands with attached polypeptides having specific target-binding properties, for example, antibodies or variable fragments of antibodies, that are selectively delivered to Chimeric Antigen Receptors (CARs) comprised of modified, non-natural NKG2D receptors on engineered mammalian cells. The targeting of surface-expressed molecules includes those of virus-infected cells that can then be attacked and ablated by engineered cells of the immunity system expressing CARs cognate to the modified, non-natural a1-a2 domains of NKG2D ligands with attached polypeptides.

CHIMERIC ANTIGEN AND T CELL RECEPTORS AND METHODS OF USE

The invention provides a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising extracellular domain disclosed herein. Some aspects of the invention relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising the extracellular domain disclosed herein. Other aspects of the invention relate to cells comprising the CAR or the TCR and their use in a T cell therapy.

GAL-1 VARIANTS HAVING IMMUNO-MODULATING PROPERTIES AND METHODS OF USING THE SAME

Galectin-1 polypeptide variants that include a mutation of the histidine residue corresponding to position 52 of the full-length amino acid sequence of native human Gal-1 as shown in SEQ ID NO: 1, the mutation being a substitution of the histidine to tyrosine or asparagine, providing resistance to acidosis otherwise resulting in deactivation of the native human Gal-1. The Galectin-1 polypeptide variants may include one or more additional mutation(s) of the cysteine residue corresponding to a position selected from 2, 16, 88, or combinations thereof of the full-length amino acid sequence of native human Gal-1 as shown in SEQ ID NO: 1, the additional mutation being a substitution of the cysteine to serine, and providing resistance to oxidation.

COMMON LYMPHATIC ENDOTHELIAL AND VASCULAR ENDOTHELIAL RECEPTOR-1 (CLEVER-1) AND USES THEREOF

... ²²²A novel protein Common Lymphatic Endothelial and Vascular Endothelial Receptor-²1 (CLEVER-1) is described. CLEVER-1 mediates leukocyte and malignant cell ²binding to vascular and lymphoid endothelial cells. CLEVER-1 is the first ²protein that has been reported to mediate both influx into and efflux from the ²lymph nodes. Also provided are methods of treating inflammation and preventing ²metastasis of malignant cells by providing an inhibitor of CLEVER-1 binding.² ...

ANTIGEN-BINDING FRAGMENTS SPECIFIC FOR DENDRITIC CELLS, COMPOSITIONS AND METHODS OF USE THEREOF ANTIGENS RECOGNIZED THEREBY AND CELLS OBTAINED THEREBY

The invention provides antigen-binding fragments specific for dendritic cell s and effective in treatment and/or diagnosing a variety of disorders. Methods of use are also provided as are methods for screening for additional such antigen-binding fragments and the products obtained thereby.

TREATMENT OF CANCER USING A CD33 CHIMERIC ANTIGEN RECEPTOR

The disclosure provides compositions and methods for treating diseases associated with expression of CD33. The disclosure also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The disclosure also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.

METHOD OF TREATING OR AMELIORATING METABOLIC DISORDERS USING CLEC-2

Methods of treating metabolic diseases and disorders using a Clec-2 extracellular domain are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, elevated glucose levels, elevated insulin levels and elevated triglyceride levels.

ПОЛУЧЕННЫЕ ИЗ СУРВИВИНА ПЕПТИДЫ, КОТОРЫЕ ИМЕЮТ СПОСОБНОСТЬ СВЯЗЫВАТЬСЯ С МНС КЛАССА II

Изобретение относится к пептиду, который способен связываться с молекулой главного комплекса гистосовместимости человека (MHC) I и II, нуклеиновой кислоте и клетке-хозяину для использования в медицине, в частности для лечения рака.

НОВЫЕ И ДЕЙСТВЕННЫЕ ПЕПТИДЫ МНС II КЛАССА, ПОЛУЧЕННЫЕ ИЗ СУРВИВИНА

Настоящее изобретение относится к пептидам, нуклеиновым кислотам и клеткам для применения в иммунотерапевтических методах. В частности, настоящее изобретение относится к иммунотерапии рака. Настоящее изобретение относится в дальнейшем к полученным из сурвивина опухолеассоциированным пептидным эпитопам цитотоксических Т-клеток (ЦТЛ), в отдельности или в комбинации с другими опухолеассоциированными пептидами, которые служат как активные фармацевтические ингредиенты для композиций вакцины, которая стимулирует антиопухолевые иммунные ответы. Настоящее изобретение специфически относится к трем новым пептидным последовательностям и их вариантам, образованным из молекул HLA класса I и II человеческих опухолевых клеток, которые могут быть использованы в вакцинных композициях для вызывания противоопухолевых иммунных ответов.

Nouvelle preparation de recepteurs du PAF et nouvelle methode de dosage du PAF

Preparation de recepteur du PAF constituee par l'association d'une preparation membranaire de recepteur du PAF avec des agents de protection appropries, tels que des inhibiteurs de proteases, par exemple. Methode de dosage du PAF present dans un echantillon biologique, qui consiste a mettre en competition un PAF marque introduit dans le milieu de dosage, avec le PAF non marque contenu dans l'echantillon biologique, pour leur occupation des sites recepteurs du PAF presents dans une preparation de recepteur egalement introduite dans le milieu de dosage. Applications au diagnostic de differents troubles.

use of peptides The CMH survivin-derived class II

MODULATION OF THE IMMUNE RESPONSE BY MEANS OF THE NKP65 RECEPTOR AND THE CLEC2A LIGAND THEREOF

The present invention relates to the NKp65 receptor protein, nucleotide sequences coding for the same, cells expressing NKp65 which are transformed, transfected, or transduced with said sequences, and the use of the protein and antibodies targeted against the same for the therapy of diseases, particularly of skin diseases. The invention further relates to the use of a substance for blocking the NKp65 receptor for the production of a pharmaceutical, particularly for the treatment and/or prevention of inflammatory or autoimmune diseases, particularly of the skin. The invention also relates to a method for the in vitro modulation of the activity of cells expressing NKp65 and/or CLEC2A, wherein the cells are brought into contact with CLEC2A or functional fragments thereof, and/or with NKp65 or functional fragments thereof. The invention further relates to the NKp65 receptor protein.

USE OF A GENETICALLY MODIFIED CELL LINE EXPRESSING FUNCTIONAL ASIALOGLYCOPROTEIN RECEPTOR IN THE PRODUCTION OF SIALYLATED GLYCOPROTEINS

The present invention is directed to the use of a cell line in the production of sialylated glycoprotein, wherein said cell line expresses functional ASGPR protein as well as to a method for the production of sialylated glycoproteins, characterized in that such a cell line is used.

HUMAN CARBOHYDRATE-ASSOCIATED PROTEINS

L'invention concerne des protéines humaines associées à des glucides (CRBAP), ainsi que des polynucléotides identifiant et codant CRBAP. Elle concerne également des vecteurs d'expression, des cellules hôtes, des anticorps, des agonistes et des antagonistes. Elle concerne également des procédés servant à diagnostiquer, traiter ou prévenir des troubles associés à l'expression de CRBAP.

COMPOSITIONS AND METHODS OF PHOSPHOLIPASE A2 RECEPTOR CHIMERIC AUTOANTIBODY RECEPTOR T CELLS

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an anti-phospholipase A2 receptor (PLA2R) autoantibody-based B cell receptor, polynucleotides encoding the CAAR, vectors comprising a polynucleotide encoding the CAAR, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified cell, e.g., a genetically modified T cell, expressing a PLA2R-CAAR wherein the expressed CAAR comprises a PLA2R extracellular domain. 1. A polynucleotide encoding a chimeric autoantibody receptor (CAAR) , wherein the CAAR comprises a phospholipase A2 receptor (PLA2R) autoantigen or fragment thereof , and optionally , a transmembrane domain , an intracellular domain of a costimulatory molecule , and/or a signaling domain.2. The polynucleotide of claim 1 , wherein the PLA2R autoantigen or fragment thereof is selected from the group consisting of:(a) an extracellular domain comprising a CysR or ricin B type lectin domain, a fibronectin type II domain, a C-type lectin domain 1 and a C-type lectin domain 2; and,(b) an extracellular domain comprising a CysR or ricin B type lectin domain, a fibronectin type II domain, a C-type lectin domain 1, a C-type lectin domain 2 and a C-type lectin domain 3.3. The polynucleotide of claim 2 , whereinthe PLA2R extracellular domain (a) is encoded by a nucleic acid sequence comprising SEQ ID NO: 8, orthe PLA2R extracellular domain (b) is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.4. The polynucleotide of claim 1 , wherein the PLA2R autoantigen or fragment thereof is selected from the group consisting of:(a) an extracellular domain comprising a cysteine rich domain,(b) an extracellular domain comprising a cysteine rich domain, a fibronectin type II domain, and a C-type lectin domain 1,(c) an extracellular domain comprising a cysteine rich domain, a fibronectin type II domain, a C-type lectin domain 1, a C-type lectin domain 2, and a C- ...

Powerful MHC-class II peptides derived from survivin

The present invention relates to peptides, nucleic acids, and cells for use in the immunotherapy of cancer. The present invention furthermore relates to survivin-derived tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention specifically relates to three novel peptide sequences and variants thereof derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 144-. (canceled)45. A pharmaceutical composition comprising: (i) at least 50% of the cells in the population of cells are CD14+ or CD11b+, and', '(ii) the population of cells has been depleted for cells expressing CD3 and CD19 and, '(a) a population of modified human cells comprising a chimeric antigen receptor (CAR), wherein(b) a pharmaceutically acceptable excipient.46. The pharmaceutical composition of claim 45 , wherein the CAR comprises an antigen binding domain claim 45 , a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule.47. The pharmaceutical composition of claim 46 , wherein the antigen binding domain comprises an anti-HER2 antigen binding domain claim 46 , an anti-mesothelin antigen binding domain claim 46 , an anti-CD19 antigen binding domain or an anti-PSMA antigen binding domain.48. The pharmaceutical composition of claim 46 , wherein the antigen binding domain of the CAR comprises an antibody selected from the group consisting of a monoclonal antibody claim 46 , a polyclonal antibody claim 46 , a synthetic antibody claim 46 , human antibody claim 46 , humanized antibody claim 46 , single domain antibody claim 46 , single chain variable fragment claim 46 , and antigen-binding fragments thereof.49. The pharmaceutical composition of claim 46 , wherein the transmembrane domain of the CAR comprises a CD8 or CD28 transmembrane domain.50. The ...

ASGR INHIBITORS

Antigen binding proteins that interact with ASGR, ASGR-1 and/or ASGR-2 are described as well as methods of making and using such antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of ASGR, ASGR-1 and/or ASGR-2 antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of interfering RNA compositions that reduce expression of ASGR, ASGR-1 and/or ASGR-2 are described.

Semaphorin receptors

The invention provides methods and compositions relating to two classes of semaphorin receptors, SR1 and SR2. The polypeptides may be produced recombinantly from transformed host cells from the disclosed SR encoding nucleic acids or purified from human cells. The invention provides isolated SR hybridization probes and primers capable of specifically hybridizing with the disclosed SR genes, SR-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

COMPOUNDS FOR MODULATING CELL NEGATIVE REGULATIONS AND BIOLOGICAL APPLICATIONS THEREOF

The invention relates to compounds for modulating cell negative regulations and biological applications thereof. It particularly relates to compounds capable of cross-linking a stimulatory receptor with a KIR (Killer-cell inhibitory receptor).

СПОСОБ ПОВЫШЕНИЯ ЧАСТОТЫ ИМПЛАНТАЦИИ ЭМБРИОНА В МАТЕРИНСКОЙ МАТКЕ МЛЕКОПИТАЮЩИХ, ПРИМЕНЕНИЕ ЭФФЕКТИВНОГО КОЛИЧЕСТВА БЕТА-ГАЛАКТОЗИД-СВЯЗЫВАЮЩЕГО ЛЕКТИНА ИЛИ ЕГО ПРОИЗВОДНЫХ, БЕТА-ГАЛАКТОЗИД-СВЯЗЫВАЮЩИЙ ЛЕКТИН ИЛИ ПРОИЗВОДНЫЕ И ПРОДУКТ

Изобретение относится к способу повышения частоты имплантации эмбриона в материнской матке млекопитающих. Способ осуществляют путем введения в матку млекопитающего эффективного количества бета-галактозид-связывающего лектина или его алкилированной формы перед предимплантационным периодом. Изобретение касается применения эффективного количества бета-галактозид-связывающего лектина или его алкилированной формы для повышения частоты имплантации эмбриона в матке млекопитающих путем осуществления способа, а также продукта для повышения частоты имплантации эмбриона в матке здоровых млекопитающих, включающего эффективное количество бета-галактозид-связывающего лектина или его алкилированной формы. Применение продукта увеличивает число имплантаций эмбрионов в материнской матке. 3 н. и 14 з.п. ф-лы, 2 табл.

УКОРОЧЕННЫЙ ТЕТРАНЕКТИН-АПОЛИПОПРОТЕИН А-I ГИБРИДНЫЙ БЕЛОК, СОДЕРЖАЩАЯ ЕГО ЛИПИДНАЯ ЧАСТИЦА И ИХ ПРИМЕНЕНИЯ

... 1. Химерный белок, который имеет аминокислотную последовательность SEQID NO: 01, или его вариант, обладающий не менее чем 70 % идентичностью последовательности относительно аминокислотной последовательности SEQID NO: 01.2. Химерный белок по п. 1 для применения в качестве лекарства.3. Химерный белок по п. 1 для применения при лечении:- острого коронарного синдрома, или- атеросклероза, или- атеросклеротических бляшек в кровеносных сосудах пациента, или- стеноза клапана у пациента, или- септического шока, или- стенокардии, или- инфаркта миокарда, или- нестабильной стенокардии, или- стенозов артерий, или- заболеваний периферических артерий (ЗПА), или- стеноза сонной артерии, или- стеноза мозговых артерий, или- стеноза коронарных артерий, или- васкулярной деменции, или- временного амавроза.4. Химерный белок по п. 1 для применения при:- индукции обратного транспорта холестерина, или- индукции контроля над бляшками, или- удалении / рассасывании / стабилизации атеросклеротических бляшек, или- перераспределении ...

ЖИВОТНЫЕ, ОТЛИЧНЫЕ ОТ ЧЕЛОВЕКА, СОДЕРЖАЩИЕ ГУМАНИЗИРОВАННЫЙ ЛОКУС ASGR 1

ЖИВОТНЫЕ, УСТОЙЧИВЫЕ К ВИРУСУ РЕПРОДУКТИВНО-РЕСПИРАТОРНОГО СИНДРОМА СВИНЕЙ

... 1. Генетически модифицированная свинья, резистентная к инфекции вирусом репродуктивно-респираторного синдрома свиней (ВРРСС), у которой, по меньшей мере, один аллель гена SIGLEC1 был инактивирован.2. Генетически модифицированная свинья, резистентная к инфекции вирусом репродуктивно-респираторного синдрома свиней (ВРРСС), у которой инактивирован, по меньшей мере, один аллель гена CD163, причем инактивация аллеля CD163 приводит к белку CD163, неспособному связывать и/или обнажать вирус репродуктивно-респираторного синдрома свиней (ВРРСС).3. Генетически модифицированная свинья по п. 1 или 2, отличающаяся тем, что оба аллеля гена SIGLEC1 были инактивированы.4. Генетически модифицированная свинья по п. 1 или 2, отличающаяся тем, что оба аллеля гена CD163 были инактивированы, причем инактивация аллелей CD163 приводит к белку CD163, неспособному связывать и/или обнажать вирус репродуктивно-респираторного синдрома свиней (ВРРСС).5. Генетически модифицированная свинья, резистентная к инфекции вирусом ...

Способ получения водорастворимой части человеческого рецептора малого сродства F @

Изобретение относится к области биотехнологии и медицины, а именно к способам получения полипептидов, пригодных для борьбы с местными и системными аллергическими реакциями. Сущность изобретения заключается в разработке способа получения водорастворимой части человеческого рецептора FcЈ малого сродства (FcЈ R). Способ включает выделение водорастворимой части связывающего IgE фактора (Fct R) из лимфобластоидных клеток, анализ ее последовательностей при помощи гидролиза, выделение получаемых при этом фрагментов и определение их последовательностей , приготовление двух проб гибридизации, выделение и идентификацию генов, кодирующих человеческий рецептор Рс малого сродства, экспрессию дДНК FcЈR, экспрессию мРНК FcЈ R, получение экспрессионного вектора, содержащего последовательности ДНК, кодирующие водорастворимый фрагмент рецептора FcЈ , экспрессию этого растворимого фрагмента в микроорганизмах или клетках млекопитающих . ё ...

USE OF CONNECTION REAGENTS AGAINST CD23 IN THE TREATMENT OF AUTOCIMMUNE DISEASES

SOLUBLE LIGANDS FOR CD40

SOLUBLE INTERLEUKIN-20 RECEPTOR

A FUSION PROTEIN

ISOLATED DENTRITI CELL DIAPHRAGM PROTEIN GENES

COMPLEMENT USED PROTEINS AND COAL HYDRATES CONTAINING COMPOSITIONS AND METHODS FOR THE PRODUCTION AND USE OF THESE COMPOSITIONS

Semaphorin receptors

Ikk2 variant, dino gene, lectin-like receptor gene, and proteins encoded thereby

PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS RESISTANT ANIMALS

Abstract: The disclosure relates to genetically modified swine wherein at least one allele of a SIGLECI gene has been inactivated and/or at least one allele of a CD 163 gene has been inactivated. Genetically modified swine having both alleles of the SIGLECI gene and/or both alleles CD 163 gene inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSV). Methods for producing such transgenic swine are also provided. WO 2012/158828 PCT/US2012/038193 Organization of the sialoadhesin gene and targeting vector design. A) 1 2 3 4 5 6 7 8 9 10 11 12 13 1415 16 17 18 19 20 21 1 kb Human 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 1920 21 Mouse C) Gln Thr Thr Trp Gly Val Ser Ser Pro Lys Asn Val Gln Gly Leu Ser Gly Ser gc cag acc aca tgg ggt gtc tcc agt ccc aag aat gtg cag ggc ttg tcg gga tcc Cys Leu Leu Ile Pro Cys Ile Phe Ser Tyr Pro Ala Asp Val Pro Val Ser Asn Gly tgc ctg ctc att ccc tgc atc ttc agc tac cct gcc gat gtc cca gtg tcc aat ggc Ile Thr Ala Trp Tyr Tyr Asp ...

A new member of the lectin superfamily

Natural killer cell compositions and immunotherapy methods for treating tumors

Several embodiments disclosed herein relate to the treatment of a tumor using immunotherapy. Several embodiments relate to the treatment of a liver tumor, such as hepatocellular carcinoma or a metastasis from another tumor location. Additional embodiments relate to combination therapies that employ Natural Killer (NK) cells engineered to express cytotoxic receptor complexes and additional anti-cancer agents to treat tumors.

Isolated dendritic cell membrane protein genes

Activation antigen cd69

Novel and powerful MHC-class II petptides derived from survivin

The present invention relates to peptides, nucleic acids, and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to survivin-derived tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention specifically relates to three novel peptide sequences and variants thereof derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

DCL-1 and uses thereof

ASGR inhibitors

Antigen binding proteins that interact with ASGR, ASGR-1 and/or ASGR-2 are described as well as methods of making and using such antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of ASGR, ASGR-1 and/or ASGR-2 antigen binding proteins. Methods of treating and preventing cardiovascular disease by administering a pharmaceutically effective amount of interfering RNA compositions that reduce expression of ASGR, ASGR-1 and/or ASGR-2 are described.

Truncated NKG2D chimeric receptors and uses thereof in natural killer cell immunotherapy

Several embodiments disclosed herein relate to the compositions comprising engineered Natural Killer (NK) cells that express a chimeric receptor, the chimeric receptor imparting to the NK cells an enhanced ability to target specific cells, such as cancerous cells or those affected by an infectious disease. Several embodiments relate to NK cells that target cells expressing natural ligands of NKG2D, where the NK cells comprise transmembrane and/or signaling domains that lead to cytotoxic and/or cytolytic effects when the NK cells bind a target cell. Uses of NK cell compositions to treat diseases are also provided for in several embodiments.

Chimeric antigen receptors targeting Fc Receptor-like 5 and uses thereof

The presently disclosed subject matter provides for methods and compositions for treating a neoplasia ( ...

PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS RESISTANT ANIMALS

Abstract of the Disclosure The invention discloses the use of the Schizochytrium limacinum and its preparation in improving the quality and yield of animal product. The deposit number of 5 Schizochytrium limacinum in the present invention is CGMCC No. 13746 in the China General Microbiological Culture Collection Center. The Schizochytrium limacinum powder produced by the Schizochytrium limacinum may increase the DHA content in an animal product, reduce the cholesterol content in an animal product, and also improve the egg production performance of poultry. This animal product with high DHA content from 10 natural sources is organic, safe, stable, and easy to be absorbed. It may be used as a safer and effective way for people to ingest natural DHA, and it may also cater to and meet consumer needs. Thus, Schizochytrium limacinum and Schizochytrium limacinum powder of the present application have a wide range of application in the field of general food and livestock breeding. WO 2012/158828 ...

Organic compounds

C-TYPE LECTIN TRANSMEMBRANE ANTIGEN EXPRESSED IN HUMAN PROSTATE CANCER AND USES THEREOF

A novel gene (designated PC-LECTIN) that is highly overexpressed in prostate cancer and its encoded protein is described. PC-LECTIN in normal human tissues is restricted to testis, but is highly expressed in prostate cancer. Consequently, PC-LECTIN provides a diagnostic and/or therapeutic target for prostate cancer.

NOVEL SIGLEC-LIKE GENE

The invention relates to nucleic acid molecules, proteins encoded by such nucleic acid molecules; and use of the proteins and nucleic acid molecules.

DIMERIZING AGENT REGULATED IMMUNORECEPTOR COMPLEXES

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

A PROTEIN BINDING NKG2D, CD16 AND A TUMOR-ASSOCIATED ANTIGEN

Multi-specific binding proteins that bind NKG2D receptor, CD16, and 5T4, a tumor-associated antigen selected from 5T4, GPNMB, FR-alpha, PAPP-A, and GPC3 are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of cancer.

NON-HUMAN ANIMALS COMPRISING A HUMANIZED ASGR1 LOCUS

Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.

CLEC9A-BASED CHIMERIC PROTEIN COMPLEXES

The present invention relates, in part, to chimeric protein complexes including an anti-Clec9A targeting moiety, a modified Fc domain, and a modified human IFNa and their use as therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the chimeric protein complexes and their use in the treatment of various diseases.

MEDICAMENT FOR MITIGATING CONDITIONS AND/OR SUPPRESSING ONSET OF PERIPHERAL NEUROPATHY INDUCED BY ANTI-MALIGNANT TUMOR AGENT

This medication is a medication for alleviating the symptoms of peripheral neuropathy caused by oxaliplatin and/or suppressing the onset of peripheral neuropathy, in a treatment that sets the intravenous administration of oxaliplatin to a human cancer patient and the withdrawal of the administration as one cycle and repeats the one cycle, and contains 0.06 mg/kg of thrombomodulin to be intravenously administered once per cycle on the first day of each cycle of the treatment as an active ingredient.

MODIFIED A1-A2 DOMAINS OF NON-NATURAL NKG2D LIGANDS THAT BIND NON-NATURAL NKG2D RECEPTORS

This present disclosure relates generally to the production of polypeptides comprised of modified a1-a2 domains of NKG2D ligands which bind specifically to a non-natural ectodomain of a non-natural NKG2D receptor and wherein heterologous molecules are attached to the modified 1-2 domains of NKG2D ligands. The present disclosure further relates to modified a1-a2 domains of NKG2D ligands attached to heterologous molecules including polypeptides, and in some embodiments, antibodies or fragments of antibodies. The present disclosure also relates to modified forms of the NKG2D receptor engineered to provide a combination of enhanced and diminished binding to non-natural and natural versions of NKG2D ligands, respectively.

METALLOPROTEASE PEPTIDE SUBSTRATES AND METHODS

The present invention describes natural or synthetic peptide substrates of the metalloproteases, ADAM8, ADAM15 and MDC-L. The invention also describes methods using these peptides to discover pharmaceutical agents that modulate these proteases.

INSERTABLE VARIABLE FRAGMENTS OF ANTIBODIES AND MODIFIED A1-A2 DOMAINS OF NKG2D LIGANDS, AND NON-NATURAL NKG2D LIGANDS THAT BIND NON-NATURAL NKG2D RECEPTORS

This application relates generally to the production of polypeptides having specific antigen-binding properties of Fv domains, for example, insertable variable fragments of antibodies, and modified a1-a2 domains of NKG2D ligands ...

METHODS AND REAGENTS FOR DETECTING SUSCEPTIBILITY TO GRAFT VERSUS HOST DISEASE OR TRANSPLANT RELATED MORTALITY

The present invention provides methods for determining the likelihood and/or severity of GvHD and the likelihood of the occurrence of transplant related mortality.

NOVEL AND POWERFUL MHC-CLASS II PEPTIDES DERIVED FROM SURVIVIN

The present invention relates to peptides, nucleic acids, and cells for use in immunotherapeutic methods. In partic-ular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to survivin-derived tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention specifically relates to three novel peptide sequences and variants thereof derived from HLA class I and class II molecules of hu-man tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

A NOVEL VACCINE THAT TARGETS TUMOR VESSELS AS AN EFFICIENT TOOL IN TUMOR THERAPY

The invention relates to a composition for the treatment of various cancers. The composition is a vaccine containing sequences of EDB, EDA, annexin A1, endosialin, C domain of tenascin C or magic roundabout (MR) or fragments thereof as single or in a combination coupled to one or several heterologous foreign carrier molecules. The vaccine will produce antibodies that are directed against self proteins which are preferentially expressed in and around tumor vessels. The vaccine is preferably administrated together with an adjuvant.

PORCINE DC-SIGN, ICAM-3 AND LSECTIN AND USES THEREOF

The present invention relates to the cloning, identification and characterization of the unique and entire genomic sequences encoding new porcine DC-SIGN and LSECtin proteins, including the novel nucleotide sequences of the full-length cDNA and genes of both pDC- SIGN gene and pLSECtin. Also provided are the nucleic acid molecules encoding newly discovered porcine ICAM-3 isoforms from porcine monocyte-derived dendritic cells and the use thereof. Specifically, the invention is drawn to an isolated nucleic acid molecule comprising a nucleotide sequence encoding one or more of porcine DC-SIGN, porcine ICAM- 3, porcine LSECtin, a complement of the nucleotide sequence or a functional, defined portion of the nucleotide sequence or a protein fusion product linked to a protein that may be of porcine or human origin. Methods for isolating and cloning the new porcine genes and for using the new nucleotide sequences in improved methods for propagating viruses, particularly enveloped viruses, are additionally ...

KIT FOR CONFIGURING TOILET FOR DISABLED PERSONS

The kit for configuring a toilet for disabled persons includes a toilet seat having a front portion having a first width and a back portion having a second width. the first width being greater than the second width, a top surface, and a bottom surface having a downward sloping wall configured for mating onto a toilet bowl of a toilet, and a mounting plate attached to the back portion of the toilet seat, the mounting plate having at least one opening configured for receiving a fastener for attaching the toilet seat onto the toilet. The top surface of the toilet seat can include a channel configured for receiving a conventional toilet seat. The kit can also include a support member, such as a floor-mounted handle bar or at least one wall-mounted handle bar, and a lid.

SOLUBLE LIGANDS FOR CD40

The present invention relates to soluble ligands for the B-cell antigen, CD40, and, in particular, to human gp39 protein and soluble ligands derived therefrom which may be used in methods of promoting Bcell proliferation.

STRUCTURED SYNTHETIC ANTIGEN LIBRARIES AS DIAGNOSTICS, VACCINES AND THERAPEUTICS

The present invention relates to "structured synthetic antigen libraries" (SSAL) composed of related peptides synthesized simultaneously in a single peptide synthesis. This "stuctured" library contrasts to those libraries previously described as "random peptide libraries" in that the order or structure within a synthetic antigen is provided by invariant amino acid residues that define the framework sequence of the synthetic antigen. The specific amino acids and their frequency of appearance at a variant locus within aligned peptide sequences is defined by the primary sequences of the several variants that make up the alignment used to construct the antigen peptide library. A method of constructing an open diagnostic, vaccine or therapeutic for a mutational infectious agent is also provided. The invention further provides the SSAL in diagnostic methods, kits vaccination methods, vaccine compositions and pharmaceutical compositions. The libraries are prepared from variable domains in proteins ...

НОВЫЕ И ДЕЙСТВЕННЫЕ ПЕПТИДЫ МНС II КЛАССА, ПОЛУЧЕННЫЕ ИЗ СУРВИВИНА

Настоящее изобретение относится к пептидам, нуклеиновым кислотам и клеткам для применения в иммунотерапевтических методах. В частности, настоящее изобретение относится к иммунотерапии рака. Настоящее изобретение относится в дальнейшем к полученным из сурвивина опухолеассоциированным пептидным эпитопам цитотоксических Т-клеток (ЦТЛ), в отдельности или в комбинации с другими опухолеассоциированными пептидами, которые служат как активные фармацевтические ингредиенты для композиций вакцины, которая стимулирует антиопухолевые иммунные ответы. Настоящее изобретение специфически относится к трем новым пептидным последовательностям и их вариантам, образованным из молекул HLA класса I и II человеческих опухолевых клеток, которые могут быть использованы в вакцинных композициях для вызывания противоопухолевых иммунных ответов.

TARGETING CYTOTOXIC CELLS WITH CHIMERIC RECEPTORS FOR ADAPTIVE IMMUNOTHERAPY

CHIMERIC RECEPTORS ANTIGENS AND T - CELL RECEPTORS AND METHODS OF THEIR APPLICATION

Chimeric antigen acceptor DAP12-T2A-CD8a-CD19scfv-NKp44 and application thereof

Method for increasing embryo implantation rate in mother's uterus in mammals, use of an effective amount of beta - galactoside - binding lectin or derivatives thereof, beta - galactoside - binding lectin or derivatives and product.

The present invention relates to a method for increasing embryo implantation rate in mother's uterus in mammals by administering to the uterus of a mammal an effective amount of beta-galactoside-binding lectin or derivatives thereof, as well as to a product comprising said lectin.

PAF RECEPTOR PREPARATION OF NEW AND NOVEL METHOD OF DOSING OF PAF

Lymphocytic virus-binding lectin LVBL

L'invention concerne un nouveau polypeptide LVBL (Lymphocytic Viruses Binding Lectin) encore appelé LSLCL (Lymphocytic Secreted Long form of C-type Lectin) et ses dérivés, le clonage de l'ADNc et les polynucléotides codant pour lesdits polypeptides, des vecteurs de clonage et/ ou d'expression incluant lesdits polynucléotides, des cellules transformées par lesdits vecteurs et des anticorps spécifiques dirigés contre lesdits polypeptides. L'invention concerne également des procédés et des kits de diagnostic d'infection virale et des composés utilisables à titre de médicament pour la prévention et/ ou le traitement de l'infection virale, en particulier par le virus HIV.

ISOLATED GENES OF MAMMAL, REACTIVE MEMBRANE PROTEINS OF RELATED

Se describen ácidos nucleicos que codifican varias proteínas de células de linfocitos de mamíferos que incluyen primates, los reactivos relacionados conlos mismos, incluyendo los anticuerpos específicos, y proteínas purificadas. También se proveenmé todos para usar dichos reactivos y equipos de diagnosticorelacionados.

ALTERNATIVE SPLICING ISOFORM OF LOX-1 PROTEIN ENCODING GENE, USES AND METHODS THEREOF

The invention relates to a new alternative splicing isoform of OLR1 gene encoding for the LOX-1 protein, uses and methods related to the treatment and to the prediction of the risk of cardiovascular diseases.

NOVEL POLYPEPTIDES

An isolated IKK2-55 gene and polypeptide; DINO gene and polypeptide; LLR-J24-stalk nucleotide and polypeptide,a polynucleotide encoding the transmembrane protein LLR-J24 and the transmembrane protein LLR-J24; a polynucleotide encoding the extracellular domain of LLR-J24 and a polypeptide which is the extracellular domain of LLR-J24; their use in a method of identifying an agonist or antagonist of such polypeptide/protein; and an antagonist or an agonist of such polypeptide/protein and its use as a pharmaceutical.

GAINAC SPECIFIC BINDING MOLECULES AND USES THEREOF

The present invention provides among others means and methods for detecting terminal GalNAc containing molecules. A preferred molecule for detecting said structures is a molecule comprising a carbohydrate binding part of MGL.

NKG2D-FC FOR IMMUNOTHERAPY

COMPOUNDS FOR MODULATING CELL NEGATIVE REGULATIONS AND BIOLOGICAL APPLICATIONS THEREOF

The invention relates to compounds for modulating cell negative regulations and biological applications thereof. It particularly relates to compounds capable of cross-linking a stimulatory receptor with a KIR (Killer-cell inhibitory receptor).

Anti-estrogen and immune modulator combinations for treating breast cancer

Compositions for treating cancers of mucosal tissues including breast, prostate, ovary, colon are disclosed which include various combinations of new or conventional anti-estrogen compounds, aromatase inhibitors, immune modulators, immune inhibitors, immune inhibitor mimicking compounds and steroid or thyroid hormones. Methods of predicting susceptibility of a cancer of mucosal origin to treatment with a composition containing an immune inhibitor or an immune inhibitor mimicking compound are also disclosed. Preferred methods include identifying in a specimen of cancer cells the presence of a Poly-Ig (Fe) receptor or Poly-Ig-like (Fc) receptor capable of binding to an immune inhibitor or an immune inhibitor mimicking compound and of mediating immune inhibition of cancer cell growth.

Methods and compositions for prognosing and detecting age-related macular degeneration

The invention provides methods and compositions for determining whether a subject is at risk of developing age-related macular degeneration, for example, the wet or neovascular form of age-related macular degeneration. The method involves determining whether the subject has a protective variant and/or a risk variant at a polymorphic site in the RORA gene. A protective or risk variant may be defined by a haplotype in the RORA gene.

Methods of Modulating Thrombocytopenia and Modified Transgenic Pigs

The application provides methods of modulating platelet uptake by liver sinusoidal endothelial cells and of modulating thrombocytopenia. Transgenic pigs modified to bind fewer platelets are provided.

NOVEL VACCINE THAT TARGETS TUMOR VESSELS AS AN EFFICIENT TOOL IN TUMOR THERAPY

The invention relates to a composition for the treatment of various cancers. The composition is a vaccine containing sequences of EDB, EDA, annexin A1, endosialin, C domain of tenascin C or magic roundabout (MR) or fragments thereof as single or in a combination coupled to one or several heterologous foreign carrier molecules. The vaccine will produce antibodies that are directed against self proteins which are preferentially expressed in and around tumor vessels. The vaccine is preferably administrated together with an adjuvant. 125-. (canceled)26. Vaccine consisting of a single or a combination of the amino acid sequences of the extra domain B of fibronectin (EDB) , the extra domain A of fibronectin (EDA) , annexin A1 , endosialin , the extra domain C of tenascin C , or magic roundabout (MR) or at least one fragment thereof , in its original or multimerized form , coupled to a carrier molecule , and a pharmaceutically acceptable adjuvant.27. Vaccine according to claim 26 , wherein the EDB claim 26 , EDA claim 26 , annexin A1 claim 26 , endosialin claim 26 , the extra domain C of tenascin C claim 26 , and magic roundabout (MR) is of human claim 26 , canine claim 26 , feline or equine origin.28. An EDB claim 26 , EDA claim 26 , annexin A1 claim 26 , endosialin claim 26 , extra domain C of tenascin C claim 26 , and magic roundabout (MR) vaccine according to for use in medicine.29. An EDB claim 27 , EDA claim 27 , annexin A1 claim 27 , endosialin claim 27 , extra domain C of tenascin C claim 27 , and magic roundabout (MR) vaccine according to for use in medicine.30. The use of a fusion protein consisting of the entire or parts of EDB claim 27 , EDA claim 27 , annexin A1 claim 27 , endosialin claim 27 , the extra domain C of tenascin C claim 27 , or magic roundabout (MR) from the species to be treated and a foreign carrier protein for production of a vaccine for medical use. A novel vaccine that targets tumor vessels as an efficient tool in tumor therapy.The present ...

Novel Enhanced Selectin Antagonists

Recombinant proteins comprised of multiple selectin binding domains derived from the glycopeptide PSGL-1, in a novel tandem configuration, are disclosed, including their fusions with immunoglobulins and/or other polypeptides. Polynucleotides encoding such proteins, compositions and kits containing such proteins, and methods of using such proteins are also disclosed.

SHORTENED TETRANECTIN-APOLIPOPROTEIN A-1 FUSION PROTEIN, A LIPID PARTICLE CONTAINING IT, AND USES THEREOF

Herein is reported a shortened tetranectin-apolipoprotein A-I fusion protein and a lipid particle comprising the shortened tetranectin-apolipoprotein A-I fusion protein as well as uses thereof. 1. A fusion protein comprising the amino acid sequence of SEQ ID NO: 01 or a variant thereof having at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 01.2. A lipid particle comprising a fusion protein of .3. The lipid particle of claim 2 , comprisinga fusion protein comprising the amino acid sequence of SEQ ID NO: 01 or a variant thereof having at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 01,a phosphatidylcholine, anda lipid.4. The lipid particle of claim 2 , comprisinga fusion protein comprising the amino acid sequence of SEQ ID NO: 01 or a variant thereof having at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 01,a first phosphatidylcholine, anda second phosphatidylcholine.5. The lipid particle of claim 4 , comprising 1-palmitoyl-2-oleoyl-phosphatidylcholine and 1 claim 4 ,2-dipalmitoyl-phosphatidylcholine.6. The lipid particle of claim 5 , wherein the molar ratio of 1-palmitoyl-2-oleoyl-phosphatidylcholine to 1 claim 5 ,2-dipalmitoyl-phosphatidylcholine is from 99:1 to 25:75.7. The lipid particle of claim 2 , wherein the fusion protein is a multimer comprising three monomers.8. The lipid particle of claim 2 , wherein the lipid particle binds to a receptor selected from the group consisting of cubilin claim 2 , Scavenger receptor class B claim 2 , type 1 (SR-BI) claim 2 , ATP-binding cassette 1 (ABCA-1) claim 2 , Lecithin-cholesterol acyltransferase (LCAT) claim 2 , Cholesteryl-ester transfer protein (CETP) claim 2 , or Phospholipid transfer protein (PLTP).9. The lipid particle of claim 4 , wherein the number of phospholipid molecules per apolipoprotein monomer in the lipid particle is from 40 to 120.10. The lipid particle of claim 9 , wherein the number of phospholipid molecules per ...

Chimeric Retinoid X Receptors and Their Use in a Novel Ecdysone Receptor-Based Inducible Gene Expression System

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/chimeric retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms. 1. A gene expression modulation system comprising: i) a DNA-binding domain that recognizes a response element associated with a gene whose expression is to be modulated; and', 'ii) an ecdysone receptor ligand binding domain; and, 'a) a first gene expression cassette that is capable of being expressed in a host cell comprising a polynucleotide sequence that encodes a first hybrid polypeptide comprising i) a transactivation domain; and', 'ii) a chimeric retinoid X receptor ligand binding domain., 'b) a second gene expression cassette that is capable of being expressed in the host cell comprising a polynucleotide sequence that encodes a second hybrid polypeptide comprising2. (canceled)3Choristoneura fumiferanaTenebrio monitorManduca sextaHeliothies virescensChironomus tentansBombyx moriDrosophila melanogasterAedes aegyptiLucilia capitataLucilia cuprinaCeratitis capitataLocusta migratoriaMyzus persicaeCeluca pugilatorBamecia argentifoliNephotetix cincticepsAmblyomma americanum. The gene expression modulation system according to claim 1 , wherein the ecdysone receptor ligand binding domain of the first hybrid polypeptide is selected from the group consisting of a spruce budworm ecdysone receptor ligand binding domain claim 1 , a beetle ecdysone receptor ligand binding domain claim 1 , a ecdysone receptor ligand binding domain claim 1 , a ecdysone receptor ligand binding domain LBD claim 1 , a midge ecdysone receptor ligand binding ...

Dendritic Cell Marker and Uses Thereof

The present invention relates to the identification of proteins located on the cell surface of dendritic cells or precursors thereof, particularly antigen presenting dendritic cells. In particular, the present invention relates to compounds such as antibodies that bind these proteins. These compounds can be used to detect and/or enrich a subset of dendritic cells or precursors thereof. These compounds can also be used to target antigens to dendritic cells or precursors thereof to modulate a humoral and/or T cell mediated immune response to an antigen, or used to target cytotoxic agents to dendritic cells or precursors thereof involved in diseased states.

METHOD FOR INCREASING EMBRYO IMPLANTATION RATE IN MOTHER'S UTERUS IN MAMMALS, USE OF AN EFFECTIVE AMOUNT OF BETA-GALACTOSIDE-BINDING LECTIN OR DERIVATIVES THEREOF, BETA-GALACTOSIDE-BINDING LECTIN OR DERIVATIVES AND PRODUCT

The present invention relates to a method for increasing embryo implantation rate in mother's uterus in mammals by administering to the uterus of a mammal an effective amount of beta-galactoside-binding lectin or derivatives thereof, as well as to a product comprising said lectin. 1. A method for increasing embryo implantation rate in the uterus of mammals , characterized in that it comprises administering to the uterus of a mammal an effective amount of beta-galactoside-binding lectin or derivatives thereof.2. Method according to claim 1 , characterized in that an amount ranging from 0.0000001 to 1.0 mg of an active form of a beta-galactoside-binding lectin or derivative thereof is administered per kilogram of body weight of the mammal.3. Method according to claim 2 , characterized in that the active form of a beta-galactoside-binding lectin or derivative is in the form of a sterile claim 2 , stable claim 2 , endotoxin-free claim 2 , isotonic carrier having a pH between 6.8 and 7.4.4. Method according to claim 3 , characterized in that the carrier is a buffered solution.5. Method according to claim 4 , characterized in that the buffered solution is selected from a saline phosphate buffered solution (PBS) or physiological serum.6. Method according to claim 1 , characterized in that the beta-galactoside-binding lectin or derivative thereof is selected from Galectin-1 claim 1 , Galectin-3 claim 1 , Galectin-9 claim 1 , Galectin-13 claim 1 , Galectin-15 or derivatives thereof.7. Method according to claim 1 , characterized in that the beta-galactoside-binding lectin or derivative thereof is supplied to the uterus of the mammal mixed with semen claim 1 , oocyte or embryo.8. Method according to claim 1 , characterized in that the beta-galactoside-binding lectin or derivative thereof is supplied to the uterus of the mammal together with semen claim 1 , oocyte or embryo claim 1 , either separately and simultaneously.9. Method according to claim 1 , characterized in that the ...

SIGLEC TRANSGENIC MICE AND METHODS OF USE THEREOF

Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, to methods of screening candidate agents that bind to and/or modulate the function and/or activity of at least one of the human genes in the transgenic non-human animals, and to methods of screening candidate agents to determine their effect on one or more activities and/or functions associated with expression of at least one of the human genes in the transgenic non-human animals. Further provided herein are methods of recapitulating a human Siglec immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human Siglec repertoire. 147.-. (canceled)48. A method of screening candidate agents , the method comprisingi) administering one or more candidate agents to a transgenic non-human animal, wherein the genome of the transgenic non-human animal comprises two or more human genes, wherein the two or more human genes are selected from the group consisting of CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, wherein the two or more human genes are expressed in one or more cells of the transgenic non-human animal, and wherein the one of more cells selected from the group consisting of myeloid cells, natural killer (NK) cells, T cells, microglia, and any combination thereof; andii) determining whether the one or more candidate agents bind to and/or modulates the function and/or activity of at least one of the two or more human genes in the transgenic non-human animal.49. A method of screening candidate agents , the method comprisingi) administering one or more candidate agents to a transgenic non-human animal, wherein the genome of the transgenic non-human animal comprises two or more human genes, wherein the two or more human genes are selected from the group consisting of CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, ...

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 144-. (canceled)45. A pharmaceutical composition comprising: wherein at least 70% of the cells in the population of cells express the CAR,', 'wherein the modified human cells are modified human macrophages and/or modified human monocytes, and, '(a) a population of modified human cells comprising a chimeric antigen receptor (CAR),'}(b) a pharmaceutically acceptable excipient.46. The pharmaceutical composition of claim 45 , wherein the CAR comprises an antigen binding domain claim 45 , a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule.47. The pharmaceutical composition of claim 45 , wherein the antigen binding domain comprises an anti-HER2 antigen binding domain claim 45 , an anti-mesothelin antigen binding domain claim 45 , an anti-PSMA antigen binding domain claim 45 , or an anti-CD19 antigen binding domain.48. The pharmaceutical composition of claim 46 , wherein the antigen binding domain of the CAR comprises an antibody selected from the group consisting of a monoclonal antibody claim 46 , a polyclonal antibody claim 46 , a synthetic antibody claim 46 , human antibody claim 46 , humanized antibody claim 46 , single domain antibody claim 46 , single chain variable fragment claim 46 , and antigen-binding fragments thereof.49. The pharmaceutical composition of claim 46 , wherein the transmembrane domain of the CAR comprises a CD8 or CD28 transmembrane domain.50. ...

NKG2D-FC FOR IMMUNOTHERAPY

Methods for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising an NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands. 1. A method for treating cancer comprising: administering to a subject having an NKG2D ligand expressing cancer a composition comprising a NKG2D-Fc chimera and a pharmaceutically acceptable carrier , in an amount effect to treat the cancer , wherein the NKG2D-Fc chimera binds a NKG2D ligand.2. The method of claim 1 , wherein the NKG2D-Fc chimera comprises a linking molecule which is not a contiguous portion of either NKG2D or Fc and which covalently joins an amino acid of NKG2D to an amino acid of Fc.3. The method of claim 2 , wherein the linking molecule is a peptide linker.4. The method of claim 3 , wherein the peptide linker is an IEGR (SEQ ID NO:1) linker.5. The method of claim 1 , wherein the NKG2D-Fc chimera comprises an NKG2D extracellular domain.6. The method of claim 1 , wherein the NKG2D-Fc chimera is a recombinant fusion protein.7. The method of claim 6 , wherein the NKG2D ligand expressing cancer is melanoma claim 6 , lung cancer claim 6 , plasma cell cancer claim 6 , leukemia claim 6 , lymphoma claim 6 , ovarian cancer claim 6 , colon cancer claim 6 , pancreatic cancer or prostate cancer.8. The method of claim 6 , further comprising treating the subject with an additional cancer therapy that is not the NKG2D-Fc chimera claim 6 , wherein the additional cancer therapy is an immunotherapy claim 6 , a radiation therapy or chemotherapy.9. The method of claim 8 , wherein the additional cancer therapy is a chemotherapy that damages DNA. This application claims the benefit of and priority under 35 U.S.C. § 119(e) to U.S. Provisional Application Ser. No. 61/138,715, filed on Dec. 18, 2008, which is incorporated by ...

GENETICALLY ENGINEERED HEMATOPOIETIC STEM CELLS AND USES THEREOF

Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins. 1. A method of treating a hematopoietic malignancy , comprising administering to a subject in need thereof: (i) a genetically engineered gene encoding CD33 that is engineered to have reduced or eliminated expression of CD33, and', '(ii) a genetically engineered gene encoding CD123 that is engineered to have reduced or eliminated expression of CD123; and, '(a) a plurality of genetically engineered hematopoietic cells (HCs) comprising(b) a therapeutically effective amount of at least one agent comprising an anti-CD33 binding domain or an anti-CD123 binding domain;wherein the hematopoietic malignancy is acute myeloid leukemia (AML).2. (canceled)3. The method of claim 1 , wherein the at least one agent comprises an anti-CD123 binding domain.4. The method of claim 3 , the at least one agent comprises a T cell comprising a CAR comprising the anti-CD123 binding domain claim 3 , or an antibody or fragment thereof comprising the anti-CD123 binding domain.5. The method of claim 4 , wherein the at least one agent further comprises an anti-CD33 binding domain.6. The method of claim 5 , wherein the at least one agent comprises a T cell comprising a CAR comprising the anti-CD33 binding domain claim 5 , or an antibody or fragment thereof comprising the anti-CD33 binding domain.7. The method of claim 1 , wherein the genetically engineered gene encoding CD123 or CD33 comprises a frameshift mutation.8. The method of claim 1 , wherein the genetically engineered HCs are genetically engineered using a CRISPR system comprising a guide nucleic acid.9. The method of claim 8 , wherein the guide nucleic acid comprises a sequence according to SEQ ID NO: 67 or a complement thereof.10. The method of ...

SHORTENED TETRANECTIN-APOLIPOPROTEIN A-1 FUSION PROTEIN, A LIPID PARTICLE CONTAINING IT, AND USES THEREOF

Herein is reported a shortened tetranectin-apolipoprotein A-I fusion protein and a lipid particle comprising the shortened tetranectin-apolipoprotein A-I fusion protein as well as uses thereof. 1. A fusion protein comprising the amino acid sequence of SEQ ID NO: 01 or a variant thereof having at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 01 , wherein the first four amino acid residues of the fusion protein are PIVN (residues 1-4 of SEQ ID NO: 01).2. A lipid particle comprising a fusion protein of .3. The lipid particle of claim 2 , further comprisinga phosphatidylcholine, anda lipid.4. The lipid particle of claim 2 , further comprisinga first phosphatidylcholine, anda second phosphatidylcholine.5. The lipid particle of claim 4 , comprising 1-palmitoyl-2-oleoyl-phosphatidylcholine and 1 claim 4 ,2-dipalmitoyl-phosphatidylcholine.6. The lipid particle of claim 5 , wherein the molar ratio of 1-palmitoyl-2-oleoyl-phosphatidylcholine to 1 claim 5 ,2-dipalmitoyl-phosphatidylcholine is from 99:1 to 25:75.7. The lipid particle of claim 2 , wherein the fusion protein is a multimer comprising three monomers.8. The lipid particle of claim 2 , wherein the lipid particle binds to a receptor selected from the group consisting of cubilin claim 2 , Scavenger receptor class B claim 2 , type 1 (SR-BI) claim 2 , ATP-binding cassette 1 (ABCA-1) claim 2 , Lecithin-cholesterol acyltransferase (LCAT) claim 2 , Cholesteryl-ester transfer protein (CETP) claim 2 , or Phospholipid transfer protein (PLTP).9. The lipid particle of claim 4 , wherein the number of phospholipid molecules per apolipoprotein monomer in the lipid particle is from 40 to 120.10. The lipid particle of claim 9 , wherein the number of phospholipid molecules per apolipoprotein monomer in the lipid particle is from 50 to 90.11. A pharmaceutical composition comprising (i) a fusion protein of claim 9 , or (ii) a lipid particle comprising a fusion protein of .12. A method fortreatment of ...

METHODS AND COMPOSITIONS FOR DECTIN-2 STIMULATION AND CANCER IMMUNOTHERAPY

Provided are methods and compositions for treating an individual with cancer by administering to the individual a composition that includes a Dectin-2 stimulating agent that stimulates Dectin-2 signaling in myeloid cells (e.g., induces Dectin-2 clustering on the cell surface), thereby stimulating an anti-cancer immune response in the individual. In some cases, the myeloid cells are tumor-associated myeloid (TAM) cells. Methods and compositions are also provided for: treating an individual with cancer via contacting a cancer cell from the individual with an alpha-mannosidase class 1 inhibitor (e.g., to increase the display and/or density of terminal mannose/mannobiose residues on the surface of target cells) in vitro or ex vivo and introducing the contacted cancer cell into the individual; stimulating an antigen presenting cell (APC) via contacting a cancer cell with an alpha-mannosidase class 1 inhibitor and contacting the APC with the inhibitor-contacted cancer cell; and stimulating an APC via contacting it with a subject Dectin-2 stimulating agent. 145-. (canceled)46. A conjugate comprising:(a) a synthetic mannobiose glycopolypeptide, or an anti-Dectin-2 antibody or antigen fragment thereof, that binds to Dectin-2 and stimulates Dectin-2 signaling, and(b) an immunomodulatory agent, a targeting agent that specifically binds to a cancer antigen, or a toll-like receptor (TLR) agonist,wherein (a) and (b) are conjugated to each other.47. The conjugate of claim 46 , wherein (b) is a TLR agonist.48. The conjugate of claim 47 , wherein the TLR agonist is a TLR 7/8 agonist.49. The conjugate of claim 46 , wherein (a) is a synthetic mannobiose glycopolypeptide.50. The conjugate of claim 49 , wherein the synthetic mannobiose glycopeptide comprises from about 8 to about 300 amino acids.51. The conjugate of claim 49 , wherein the synthetic mannobiose glycopolypeptide has at least 35% glycan density.52. The conjugate of claim 49 , wherein the synthetic mannobiose ...

DIMERIZING AGENT REGULATED IMMUNORECEPTOR COMPLEXES

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith. 1. A non-natural cell comprising:(a) a first polypeptide comprising: a first multimerization domain polypeptide or variant thereof; a first transmembrane domain; a first costimulatory domain; and/or a primary signaling domain; and(b) a second polypeptide comprising: an extracellular binding domain; a second multimerization domain polypeptide or variant thereof; a second transmembrane domain; and a second costimulatory domain;wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the first and second multimerization domains.2. The non-natural cell of claim 1 , wherein the first and second multimerization domains are different.3. The non-natural cell of or claim 1 , wherein the first and second costimulatory domains are different.4. The non-natural cell of any one of to claim 1 , wherein the first multimerization domain and the second multimerization domain associate with a bridging factor selected from the group consisting of: rapamycin or a rapalog thereof claim 1 , coumermycin or a derivative thereof claim 1 , gibberellin or a derivative thereof claim 1 , abscisic acid (ABA) or a derivative thereof claim 1 , methotrexate or a derivative thereof claim 1 , cyclosporin A or a derivative thereof claim 1 , FK506/cyclosporin A (FKCsA) or a derivative thereof claim 1 , and trimethoprim (Tmp)-synthetic ligand for FK506 binding protein (FKBP) (SLF) or a derivative thereof.5. The non-natural cell of any one of to claim 1 , wherein the first multimerization domain and the second multimerization domain are a pair selected from the group consisting of: FKBP and FKBP-rapamycin binding (FRB) ...

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 130-. (canceled)31. A modified cell comprising a chimeric antigen receptor (CAR) , wherein the CAR comprisesan anti-HER2 antigen binding domain, an anti-PSMA binding domain, or an anti-mesothelin antigen binding domain,a transmembrane domain, andan intracellular domain of a stimulatory and/or co-stimulatory molecule, and wherein the modified cell is a macrophage or a monocyte.32. The modified cell of claim 31 , wherein the CAR further comprises a hinge domain.33. The modified cell of claim 32 , wherein the hinge domain comprises a CD8 hinge domain or an Ig hinge domain.34. The modified cell of claim 31 , wherein the transmembrane domain comprises a CD8 transmembrane domain claim 31 , a CD64 transmembrane domain claim 31 , a CD16 transmembrane domain claim 31 , a TLR1 transmembrane domain claim 31 , a TLR2 transmembrane domain claim 31 , a TLR4 transmembrane domain claim 31 , a TLR5 transmembrane domain claim 31 , or a TLR6 transmembrane domain.35. The modified cell of claim 31 , wherein the intracellular domain comprises dual signaling domains.36. The modified cell of claim 31 , wherein the intracellular domain comprises a CD3 zeta intracellular domain claim 31 , an FcεRI common γ subunit intracellular domain claim 31 , a Dectin-1 intracellular domain claim 31 , a CD16 intracellular domain claim 31 , a TLR1 intracellular domain claim 31 , a TLR2 intracellular domain claim 31 , a TLR4 intracellular domain ...

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 144-. (canceled)45. A modified macrophage or monocyte comprising a chimeric antigen receptor (CAR) , 'wherein the modified macrophage or monocyte exhibits targeted effector activity, and', 'wherein the CAR comprises an antigen binding domain, a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule,'}wherein, after exposure to one or more suppressive cytokines, the modified macrophage or monocyte maintains targeted effector activity.46. The modified macrophage or monocyte of claim 45 , wherein one or more suppressive cytokines comprise IL-4 claim 45 , IL-10 claim 45 , and/or IL-13.47. The modified macrophage or monocyte of claim 45 , wherein the antigen binding domain of the CAR comprises an antibody selected from the group consisting of a monoclonal antibody claim 45 , a polyclonal antibody claim 45 , a synthetic antibody claim 45 , human antibody claim 45 , humanized antibody claim 45 , single domain antibody claim 45 , single chain variable fragment claim 45 , and antigen-binding fragments thereof.48. The modified macrophage or monocyte of claim 45 , wherein the transmembrane domain of the CAR comprises a CD8 or CD28 transmembrane domain.49. The modified macrophage or monocyte of claim 45 , wherein the intracellular domain of the CAR comprises dual signaling domains.50. The modified macrophage or monocyte of claim 45 , wherein the intracellular domain of the CAR ...

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 144-. (canceled)45. A method of treating a malignancy in a subject , comprising:administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a modified cell comprising a chimeric antigen receptor (CAR),wherein the CAR comprises an antigen binding domain, a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule,wherein the antigen binding domain targets a tumor antigen, andwherein the modified cell is a human macrophage or human monocyte.46. The method of claim 45 , wherein the tumor antigen is Receptor tyrosine-protein kinase ERBB2 (HER2) claim 45 , prostate-specific membrane antigen (PSMA) claim 45 , CD19 claim 45 , or mesothelin.47. The method of claim 45 , wherein the malignancy is or comprises: carcinoma claim 45 , blastoma claim 45 , sarcoma claim 45 , leukemia claim 45 , a lymphoid malignancy claim 45 , or melanoma.48. The method of claim 45 , wherein the antigen binding domain of the CAR comprises an antibody selected from the group consisting of a monoclonal antibody claim 45 , a polyclonal antibody claim 45 , a synthetic antibody claim 45 , human antibody claim 45 , humanized antibody claim 45 , single domain antibody claim 45 , single chain variable fragment claim 45 , and antigen-binding fragments thereof.49. The method of claim 45 , wherein the transmembrane domain of the CAR comprises a CD8 or CD28 ...

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 144-. (canceled)45. A modified cell comprising a chimeric antigen receptor (CAR) ,wherein the CAR comprises an antigen binding domain, a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule, andwherein the modified cell expresses the CAR and possesses targeted effector activity,wherein the modified cell comprises a macrophage or a monocyte, andwherein the modified cell comprises a lentiviral component.46. The modified cell of claim 45 , wherein the modified cell exhibits reduced SIRPα activity relative to an unmodified monocyte or macrophage.47. The modified cell of claim 45 , wherein the antigen binding domain of the CAR comprises an antibody selected from the group consisting of a monoclonal antibody claim 45 , a polyclonal antibody claim 45 , a synthetic antibody claim 45 , human antibody claim 45 , humanized antibody claim 45 , single domain antibody claim 45 , single chain variable fragment claim 45 , and antigen-binding fragments thereof.48. The modified cell of claim 45 , wherein the antigen binding domain of the CAR is selected from the group consisting of an anti-CD19 antibody claim 45 , an anti-HER2 antibody claim 45 , an anti-mesothelin antibody claim 45 , an anti-PSMA antibody claim 45 , and a fragment thereof.49. The modified cell of claim 45 , wherein the transmembrane domain of the CAR comprises a CD8 or CD28 transmembrane domain.50. The modified cell ...

Novel Substitution Mutant Receptors and Their Use in an Ecdysone Receptor-Based Inducible Gene Expression System

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel nuclear receptors comprising a substitution mutation and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene within a host cell using this inducible gene expression system. 19.-. (canceled)10. An isolated polynucleotide encoding a Group B nuclear receptor ligand binding domain comprising a substitution mutation at a position selected from the group consisting of(a) 401 or 429 of SEQ ID NO: 1,(b) 401 and 429 of SEQ ID NO: 1,(c) 337, 462, 470, or 473 of SEQ ID NO: 2,(d) 450, 451, and 452 of SEQ ID NO: 2,(e) 455, 456, 457, and 458 of SEQ ID NO: 2,(f) 475, 476, 477, 478, and 479 of SEQ ID NO: 2, and(g) 481, 482, and 483 of SEQ ID NO: 2.11. The isolated polynucleotide according to claim 10 , wherein the codon mutation results in a substitution mutation selected from the group consisting of(a) E401D or G429S of SEQ ID NO: 1,(b) E401D and G429S of SEQ ID NO: 1,(c) T337S, S470A, or T473E of SEQ ID NO: 2,(d) D450E, A451V, and K452R of SEQ ID NO: 2,(e) S455K, N456S, P457A, and S458Q of SEQ ID NO: 2,(f) C475T, K476R, Q477T, K478T, and Y479H of SEQ ID NO: 2, and(g) E481D, Q482E, and Q483P of SEQ ID NO: 2.12. An expression vector comprising the isolated polynucleotide of operatively linked to a transcription regulatory element.13. A host cell comprising the expression vector of claim 12 , wherein the transcription regulatory element is operative in the host cell.14. An isolated polypeptide encoded by the isolated polynucleotide according to .1517-. (canceled)18. A method of modulating the expression of a gene in a host cell comprising the steps of: [ (1) a DNA-binding domain that recognizes a response element associated with a gene whose expression is to be modulated; and', '(2) a first nuclear receptor ligand ...

COMPOSITION AND METHOD FOR INHIBITING AMYLOID BETA ACCUMULATION AND/OR AGGREGATION

Disclosed herein is an amyloid β accumulation and/or aggregation inhibitor. A technique for inhibiting amyloid β accumulation and/or aggregation by concurrently introducing Nurr1 and Foxa2 genes and introducing the co-expression of the genes is also provided. When used, the composition can be applied to the prevention or treatment of a neurodegenerative disease caused by amyloid β accumulation and/or aggregation, such as Alzheimer's disease. 122.-. (canceled)23. A method for inhibiting amyloid β accumulation and/or aggregation in a subject , comprising the step of:administering to the subject a therapeutically effective amount of a composition comprising Nurr1 and Foxa2 genes, wherein the administration inhibits amyloid β accumulation.24. The method of claim 23 , wherein the Nurr1 and Foxa2 genes are carried by a vector.25. The method of claim 24 , wherein the vector is viral vector.26. The method of claim 25 , wherein the viral vector comprises an adeno-associated virus claim 25 , lentivirus claim 25 , adenovirus claim 25 , herpes virus claim 25 , retrovirus claim 25 , vaccinia virus claim 25 , or poxvirus vector.27. The method of claim 24 , wherein the vector is a non-viral vector.28. The method of claim 26 , wherein the non-viral vector comprises a plasmid claim 26 , RNA molecule claim 26 , or lipofection vector.29. The method of claim 23 , wherein the composition comprises neurons claim 23 , neuronal stem cells claim 23 , or glia claim 23 ,and wherein the Nurr1 and Foxa2 genes have been introduced into the neurons, neuronal stem cells, or glia.30. The method of claim 26 , wherein the glia are astrocytes or microglia.31. The method of claim 23 , wherein the subject is a mammalian subject.32. The method of claim 23 , wherein the effective amount of the composition comprises from 5×10to 5×10viral genomes each of Nurr1 and Foxa2 per dose administered to the subject.33. The method of claim 23 , wherein the administration of the effective amount is directly to the ...

BREAST AND OVARIAN CANCER VACCINES

The compositions described herein include an epitope of a peptide that may elicit an immune response in a subject following administration. The compositions may comprise nucleic acids. The compositions may comprise peptides. The methods described herein include administering a composition comprising an epitope of a peptide to a subject in need thereof. 1223-. (canceled)224. A composition comprising a plurality of epitopes , wherein the epitopes comprise an amino acid sequence having at least 95% sequence identity to the IGFBP-2 amino acid sequence of SEQ ID NO: 54 , an amino acid sequence having at least 95% sequence identity to the Survivin amino acid sequence of SEQ ID NO: 85 , an amino acid sequence having at least 95% sequence identity to the HIF1A amino acid sequence of SEQ ID NO: 87 , and an amino acid sequence having at least 95% sequence identity to the IGF1R amino acid sequence of SEQ ID NO: 73.225. A composition comprising a fusion protein having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 89 , wherein the fusion protein comprises a plurality of epitopes , and wherein the plurality of epitopes comprises the amino acid sequences of SEQ ID NO: 54 , SEQ ID NO: 73 , SEQ ID NO: 85 and SEQ ID NO: 87.226. The composition of claim 225 , wherein the fusion protein has at least 99% sequence identity to SEQ ID NO: 89.227. The composition of claim 225 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 89.228. The composition of claim 225 , wherein the fusion protein consists of the amino acid sequence of SEQ ID NO: 89.229. The composition of claim 225 , further comprising a pharmaceutically acceptable carrier claim 225 , an adjuvant claim 225 , a chemotherapeutic agent claim 225 , or a combination thereof.230. The composition of claim 229 , wherein the adjuvant is GM-CSF.231. The composition of claim 229 , wherein the chemotherapeutic agent is cisplatin.232. The composition of claim 225 , wherein the plurality of ...

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 1. A modified cell comprising a chimeric antigen receptor (CAR) ,wherein the CAR comprises an antigen binding domain, a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule, andwherein the modified cell has at least one upregulated M1 marker and/or at least one downregulated M2 marker relative to an unmodified cell, andwherein the modified cell is a macrophage or monocyte.2. The modified cell of claim 1 , wherein the at least one upregulated M1 marker is or comprises HLA DR claim 1 , CD86 claim 1 , CD80 claim 1 , or PDL1.3. The modified cell of claim 1 , wherein the at least one downregulated M2 marker is or comprises CD206 or CD163.4. The modified cell of claim 1 , wherein the antigen binding domain of the CAR comprises an antibody selected from the group consisting of a monoclonal antibody claim 1 , a polyclonal antibody claim 1 , a synthetic antibody claim 1 , human antibody claim 1 , humanized antibody claim 1 , single domain antibody claim 1 , single chain variable fragment claim 1 , and antigen-binding fragments thereof.5. The modified cell of claim 1 , wherein the transmembrane domain of the CAR comprises a CD8 or CD28 transmembrane domain.6. The modified cell of claim 1 , wherein the intracellular domain of the CAR comprises dual signaling domains.7. The modified cell of claim 1 , wherein the intracellular domain of the CAR comprises a CD3 zeta intracellular ...

NKG2D CHIMERIC ANTIGEN RECEPTORS

Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill transformed and infected cells. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs. 1. A chimeric antigen receptor (CAR) polypeptide , comprising a NKG2D ectodomain , a transmembrane domain , and either an intracellular signaling domain but not a co-stimulatory signaling region , or a co-stimulatory signaling region but not an intracellular signaling domain.2. The polypeptide of claim 1 , wherein the NKG2D ectodomain comprises an amino acid sequence having at least 65% claim 1 , 70% claim 1 , 71% claim 1 , 72% claim 1 , 73% claim 1 , 74% claim 1 , 75% claim 1 , 76% claim 1 , 77% claim 1 , 78% claim 1 , 79% claim 1 , 80% claim 1 , 81% claim 1 , 82% claim 1 , 83% claim 1 , 84% claim 1 , 85% claim 1 , 86% claim 1 , 87% claim 1 , 88% claim 1 , 89% claim 1 , 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% claim 1 , 94% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% claim 1 , or 100% sequence identity SEQ ID NO:1 claim 1 , or a fragment thereof of at least 100 claim 1 , 110 claim 1 , 120 claim 1 , 130 claim 1 , 135 claim 1 , 136 claim 1 , 137 claim 1 , 138 claim 1 , 139 claim 1 , 140 claim 1 , 141 claim 1 , 142 claim 1 , or 143 amino acids that can bind induced-self proteins.3. The polypeptide of claim 1 , wherein the costimulatory signaling region comprises the cytoplasmic domain of a costimulatory molecule selected from the group consisting of CD27 claim 1 , CD28 claim 1 , 4-1BB claim 1 , OX40 claim 1 , CD30 ...

PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS RESISTANT ANIMALS

The present invention generally relates to genetically modified swine wherein at least one allele of a SIGLEC1 gene has been inactivated and/or at least one allele of a CD163 gene has been inactivated. Genetically modified swine having both alleles of the SIGLEC1 gene and/or both alleles CD163 gene inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSV). Methods for producing such transgenic swine are also provided. 1. A genetically modified swine comprising an inactivating mutation in an allele of a CD163 gene.2. The genetically modified swine of claim 1 , wherein the swine comprises inactivating mutations in both alleles of the CD163 gene.3. The genetically modified swine of claim 1 , wherein the mutation alters the expression or activity of CD163.4. The genetically modified swine of claim 2 , wherein the mutations alter the expression or activity of CD163.5. The genetically modified swine of claim 1 , wherein the mutation comprises an insertion claim 1 , a deletion claim 1 , a frame shift mutation claim 1 , a nonsense mutation claim 1 , a missense mutation claim 1 , or a point mutation.6. The genetically modified swine of claim 2 , wherein the mutations comprise insertions claim 2 , deletions claim 2 , frame shift mutations claim 2 , nonsense mutations claim 2 , missense mutations claim 2 , point mutations claim 2 , or a combination thereof.7. The genetically modified swine of claim 1 , wherein the mutation comprises a partial deletion or a complete deletion of the allele.8. The genetically modified swine of claim 2 , wherein the mutations comprise partial deletions of the alleles claim 2 , complete deletions of the alleles claim 2 , or a combination thereof.9. The genetically modified swine of claim 1 , wherein the mutation comprises a complete knockout of the CD163 allele.10. The genetically modified swine of claim 2 , wherein the mutations comprise complete knockouts of the CD163 alleles.11. The genetically modified swine of ...

Use of hla-b27 homodimers for cancer treatment

The invention relates to a HLA-B27 Fc open conformer or a HLA-B27 Fc fusion protein for use in the treatment or prevention of cancer. The Fc open conformer comprises or consists of a first and a second monomer, and each monomer comprises a HLA-B27 chain. The Fc fusion protein further comprises a protein stabilizing polypeptide sequence and optionally an amino acid linker. Further aspects of the invention provide combination medicaments comprising the HLA-B27 Fc open conformer and immune checkpoint inhibitors.

ANTIBODIES TO GALECTIN-3 AND METHODS OF USE THEREOF

Provided herein are compositions, methods, and uses involving antibodies that immunospecifically bind the Galactin-3 (LGALS3) carbohydrate binding domain (CBD). Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer. 1. An antibody or an antigen-binding fragment thereof , wherein the antibody or an antigen-binding fragment thereof immunospecifically binds to a Galectin-3 (LGALS3) carbohydrate binding domain (CBD) , wherein the LGALS3 CBD comprises SEQ ID NO: 27.2. (canceled)3. The antibody or antigen-binding fragment thereof of claim Error! Reference source not found. , wherein the antibody or antigen-binding fragment thereofinhibits in vitro invasion of tumor cells in a Matrigel invasion assay, optionally wherein the tumor cells are ovarian tumor cells;inhibits binding of LGALS3 to a glycosylated cell surface protein, a glycosylated cell surface receptor, or a glycosylated growth factor receptor,inhibits binding of LGALS3 to glycosylated mucin-1 (MUC1), mucin-4 (MUC4), mucin-16 (MUC16), a disialoganglioside, GD2, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), insulin-like growth factor receptor (IGFR), an integrin and CTLA4, optionally wherein the glycosylated MUC16 is N-glycosylated at Asn1800 or Asn1806, orinhibits growth of a tumor that expresses a glycosylated form of MUC16.4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a monoclonal antibody or a humanized antibody claim 1 , optionally wherein the antibody or antigen-binding fragment thereof is a humanized form of a rodent antibody.12. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) claim 1 , comprising:(a) a VH complementarity determining region (CDR)1 comprising the ...

CO-CRYSTALS OF NURR1-LBD IN COMPLEX WITH A CYCLOPENTENONE PROSTAGLANDIN AND MODULATORS OF NURR1

Co-crystals comprising the Nuclear receptor related 1 protein-ligand binding domain (Nurr1-LBD) and a cyclopentenone prostaglandin are provided. Also provided are methods of identifying or designing Nurr1-modulating ligands and compounds based on the crystal structures described herein as well as the applications of said ligands and compounds as Nurr1 modulators or medicaments. 1. A co-crystal comprising a Nuclear receptor related 1 protein-ligand binding domain (Nurr1-LBD) and a cyclopentenone prostaglandin.2. The co-crystal of claim 1 , wherein the Nurr1-LBD has the amino acid sequence set forth in SEQ ID NO:1.3. The co-crystal of claim 1 , wherein the cyclopentenone prostaglandin is selected from the group consisting of prostaglandin A1 (PGA1) claim 1 , prostaglandin A2 (PGA2) claim 1 , 15-deoxy-Δ12 claim 1 ,14-prostaglandin J2 (15-d-Δ12 claim 1 ,14-PGJ2) claim 1 , Δ12-Prostaglandin J2 (Δ12-PGJ2) claim 1 , and Prostaglandin J2 (PGJ2).4. The co-crystal of claim 1 , wherein the Nurr1-LBD has the amino acid sequence set forth in SEQ ID NO:1 claim 1 , the cyclopentenone prostaglandin is PGA1 claim 1 , and wherein the co-crystal is described by the atomic coordinates deposited at the Protein Data Bank (PDB) under accession number 5Y41.5. The crystalline form co-crystal of claim 1 , wherein the Nurr1-LBD has the amino acid sequence set forth in SEQ ID NO:1 claim 1 , the cyclopentenone prostaglandin is PGA2 claim 1 , and wherein the co-crystal is described by the atomic coordinates deposited at the Protein Data Bank (PDB) under accession number 5YD6.6. A non-transitory computer readable medium storing a program causing a computer to execute a method for identifying or designing a compound that fits within or binds to a Nurr1-LBD or a portion thereof claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'providing the structure of the Nurr1-LBD or a portion thereof as defined in the co-crystal of ;'}providing the structure of a candidate ...

Quadricistronic system comprising a homing receptor and chimeric antigen receptor for stable genetic modification of cellular immunotherapies

Provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) a homing receptor, ii) Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Further provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) IL-12 and/or TGF-beta trap, ii) an Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Also provided are compositions and kits comprising the modified NK-92® cells, as well as methods of treating cancer using the modified cells.

Activating Chimeric Receptors and Uses Thereof In Natural Killer Cell Immunotherapy

Current invention relates to a polynucleotide encoding activating chimeric receptors comprising engineered Natural Killer Group 2 member C (NKG2C) having enhanced affinity for HLA class I histocompatibility antigen alpha chain E (HLA-E)/peptide complex or an extracellular receptor domain of NKG2A coupled to an effector domain. It also relates to NK cells expressing such constructs and the use of these NK cells to induce cytotoxicity. It further exemplifies that the NK cells expressing polynucleotide encoding NKG2C (SIIS)/CD94/DAP12 or NKG2C/CD94/4-1 BB/CD3z showed enhanced NK cytotoxicity against cancer cells. 148.-. (canceled)49. A polynucleotide encoding an activating chimeric receptor that binds HLA class I histocompatibility antigen , alpha chain E (HLA-E)/peptide complex , wherein the activating chimeric receptor transduces activation and/or costimulatory signals following binding to the HLA-E/peptide complex , wherein the activating chimeric receptor comprises: wherein the fragment of NKG2A is coupled to an effector domain comprising a transmembrane region and an intracellular signaling domain,', 'wherein the transmembrane domain comprises a CD8α transmembrane domain and the intracellular signaling domain comprises 4-1BB and CD3zeta,', 'wherein native NKG2A transduces inhibitory signals following binding to HLA-E/peptide complex, and', 'wherein the fragment of NKG2A transduces activation and/or costimulatory signals following binding to HLA-E/peptide complex., 'an extracellular receptor domain, wherein said extracellular receptor domain comprises a fragment of Natural Killer Group 2 member A (NKG2A),'}50. The polynucleotide of claim 49 , wherein the activating chimeric receptor is encoded by a nucleic acid having at least 95% homology to the sequence of SEQ ID NO: 61.51. The polynucleotide of claim 49 , wherein the activating chimeric receptor comprises the amino acid sequence of SEQ ID NO: 62.52. The polynucleotide claim 49 , wherein the activating chimeric ...

FLT3L-BASED CHIMERIC PROTEINS

The present invention relates, inter alia, to compositions and methods, including chimeric proteins comprising an extracellular domain of FMS like tyrosine kinase 3 ligand (FLT3L) and an extracellular domain of a Type II transmembrane protein that find use in the treatment of disease, such as cancer. 149.-. (canceled)51. The chimeric protein of claim 50 , wherein the first domain comprises substantially the entire extracellular domain of FLT3L.52. The chimeric protein of claim 50 , wherein the second domain comprises substantially the entire extracellular domain of 4-1BBL.53. The chimeric protein of claim 50 , wherein the extracellular domain of FLT3L is capable of activating an immune stimulatory signal.54. The chimeric protein of claim 50 , wherein the extracellular domain of 4-1BBL is capable of activating an immune stimulatory signal.55. The chimeric protein of claim 50 , wherein the chimeric protein is capable of forming a stable synapse between cells.56. The chimeric protein of claim 55 , wherein the stable synapse between cells provides a spatial orientation that favors tumor reduction.57. The chimeric protein of claim 56 , wherein the spatial orientation positions T cells to attack tumor cells.58. The chimeric protein of claim 50 , wherein binding of either or both of the extracellular domains to its respective binding partner occurs with slow off rates (K) claim 50 , which provides a long interaction of a receptor and its ligand.59. The chimeric protein of claim 50 , wherein the long interaction provides immune cell proliferation and allows for anti-tumor attack.60. The chimeric protein of claim 50 , wherein the chimeric protein is capable of causing activation of antigen presenting cells and/or capable of enhancing the ability of antigen presenting cells to present antigen.61. The chimeric protein of claim 60 , wherein the antigen presenting cells are CD103+ antigen presenting cells claim 60 , optionally claim 60 , CD11c+CD103+ cells.62. The chimeric ...

NKT-LIKE CELL SUBPOPULATION AND METHOD OF USING THE SAME IN THE TREATMENT OF TUMOR

The disclosure discloses a kind of new NKT-like cell subpopulation, a therapeutical composition comprising the NKT-like cell subpopulation, and the medical use thereof. The disclosure also provides a preparation method of the NKT-like cell subpopulation. The disclosed NKT-like cell subpopulation has a strong antitumor effect, and can be adoptive transferred into a subject to treat the tumor in the subject after in vitro cultured and amplified. 1. An isolated NKT-like cell subpopulation , comprising NKT-like cells expressing CD8 , CD3 and TCRαβ , wherein the NKT-like cell subpopulation is isolated from a mammal subject.2. The NKT-like cell subpopulation according to claim 1 , comprising 50% or more claim 1 , preferably 60% or more claim 1 , more preferably 70% or more claim 1 , most preferably 80% or more of the NKT-like cells expressing CD8 claim 1 , CD3 and TCRαβ.3. The NKT-like cell subpopulation according to claim 1 , wherein the NKT-like cells further express CD56 claim 1 , but not Vα24 TCR.4. The NKT-like cell subpopulation according to claim 1 , wherein the NKT-like cells further express CD161c claim 1 , but not Vα14 TCR.5. The NKT-like cell subpopulation according to claim 1 , wherein the mammal is a species selected from the group consisting of bovidae claim 1 , equidae claim 1 , felidae claim 1 , canidae claim 1 , leporidae claim 1 , suidae claim 1 , camelidae claim 1 , rodent and primate claim 1 , preferably being a cattle claim 1 , a horse claim 1 , a dog claim 1 , a goat claim 1 , a sheep claim 1 , a pig claim 1 , a camel claim 1 , a rat claim 1 , a mouse claim 1 , a monkey or a human.6. A therapeutical composition comprising mammal NKT-like cells expressing CD8 claim 1 , CD3 and TCRαβ as a main active ingredient claim 1 , and a pharmaceutical acceptable carrier claim 1 , diluent claim 1 , excipient claim 1 , and/or additive.7. The composition according to claim 6 , wherein the NKT-like cells further express CD56 claim 6 , but not Vα24 TCR.8. The ...

TREATMENT OF CANCER USING A CD33 CHIMERIC ANTIGEN RECEPTOR

The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain. 124.-. (canceled)25. An isolated chimeric antigen receptor (CAR) polypeptide , wherein the CAR comprises a CD33 binding domain , a transmembrane domain , and an intracellular signaling domain comprising a costimulatory domain and/or a primary signaling domain , and wherein said CD33 binding domain comprises:(i) a heavy chain variable region comprising: 'a light chain variable region comprising:', 'a heavy chain complementary determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 274, a heavy chain complementary determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 283, and a heavy chain complementary determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 292; and'}a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 301, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 310, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 319;(ii) a heavy chain variable region comprising: 'a light chain variable region comprising:', 'a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 328, a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 337, and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 346; and'}a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 355, a light chain complementarity determining region 2 ...

COMPOSITIONS AND METHODS FOR ENHANCING THE PLURIPOTENCY OF STEM CELLS

Described herein is the finding that increasing the frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. As the potency increases, even a whole animal can be produced from a single ES cell injected into a 4N blastocyst at an unexpectedly high success rate. The studies disclosed herein indicate that ES cells acquire higher potency by going through the transient Zscan4 activation state more frequently than the regular state. Particularly disclosed herein is the finding that the constitutive presence of Zscan4-ERT2, even in the absence of its usual activator tamoxifen, can increase the frequency of endogenous Zscan4 activation in ES cells, resulting in the increase of developmental potency of the ES cells. Accordingly, provided herein are Zscan4-ERT2 fusion proteins and nucleic acid molecules and vectors encoding Zscan4-ERT2 fusion proteins. Further provided are methods of prolonging and/or enhancing stem cell pluripotency using the disclosed Zscan4-ERT2 nucleic acid molecules and fusion proteins. 1. A recombinant polypeptide selected from a Zscan4-ERT2 fusion protein and a Zscan4-ΔC protein.2. The recombinant polypeptide of claim 1 , wherein the Zscan4 or the Zscan4-ΔC protein comprises mouse Zscan4c claim 1 , mouse Zscan4d claim 1 , mouse Zscan4f or human ZSCAN4 claim 1 , or a functional fragment or variant thereof.3. The recombinant polypeptide of claim 1 , comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23.4. The recombinant polypeptide of claim 1 , wherein the Zscan4-ΔC protein comprises mouse Zscan4c claim 1 , mouse Zscan4d claim 1 , mouse Zscan4f or human ZSCAN4 comprising a deletion of at least one zinc finger domain.5. An isolated cell comprising the recombinant polypeptide of .6. The isolated cell of claim 5 , which is a stem cell.7. The isolated cell of claim 6 , which is an ES cell or an iPS cell.8. The ...

A RECOMBINANT CHIMERIC PROTEIN FOR SELECTINS TARGETING

The invention discloses a recombinant protein (P-selectin glycoprotein ligand-1 and Neural Retina-specific Leucine Zipper) PSGL-1-NRL chimeric protein comprising a Selectin Binding domain and a non-covalent dimerization domain, which is a leucine zipper and is more preferably the leucine zipper domain of the human or mouse Neural Retina-specific Leucine Zipper. The chimeric protein further comprises a covalent dimerization domain with at least one cysteine suitable to form a disulfide bridge with another chimeric protein to form a homodimer. In the chimeric protein, the PSGL-1 domain corresponds to the extracellular region of Human PSGL-1 and is more preferably the selectin binding region of the mature protein. The chimeric protein is correctly post-translationally modified and is efficiently expressed in a mammalian system. It is sulfated, O-linked glycosylated and sialylated and binds P, E and L selectin, allowing in vivo and in vitro targeting for diagnostic or therapeutic purposes. 1. A recombinant chimeric P-Selectin Glycoprotein Ligand-1 (PSGL-1) protein comprising at least: a selectin Binding domain comprising at least aa 5-16 of SEQ ID NO:11 (mature PSGL-1 sequence) , leucine zipper domain comprising an amino acid sequence at least 90% homologous or identical to aa 187-208 of SEQ ID NO:12 (Neural Retina-specific Leucine Zipper) and a disulfide bonds promoting region.2. The recombinant chimeric PSGL-1 protein according to wherein the selectin Binding domain comprises at least an 1-47 of SEQ ID NO:11 (PSGL-1 sequence).3. The recombinant chimeric PSGL-1 protein according to wherein said leucine Zipper comprises an amino acid sequence at least 90% homologous or identical to aa 181-215 of SEQ ID NO:12.4. The recombinant chimeric PSGL-1 protein according to wherein said disulfide bonds promoting region comprises an amino acid sequence defined by the following general formula:{'br': None, 'sub': 1', '2', '3, 'i': n', 'm, '(X)-C(X)-(X)'} [{'sub': 1', '2, 'X, ...

PEPTIDES

The present invention relates to novel peptides derived from Nuclear receptor subfamily 0 group B member 1 (NR0B1), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer. 1. A polypeptide comprising:(a) the amino acid sequence of any one of SEQ ID NOS: 1-19, or(b) the amino acid sequence of any one of SEQ ID NOs: 1-19 with the exception of 1, 2 or 3 amino acid substitutions and/or 1, 2 or 3 amino acid insertions, and/or 1, 2 or 3 amino acid deletions,wherein the polypeptide is capable of forming a complex with a Major Histocompatibility Complex (MHC) molecule.2. The polypeptide of claim 1 , wherein the polypeptide consists of from 8 to 16 amino acids.3. The polypeptide of claim 1 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NOs 1-19.4. A complex of the polypeptide of and a Major Histocompatibility Complex (MHC) molecule.5. The complex of claim 4 , wherein the MHC molecule is MHC class I.6. A nucleic acid molecule encoding the polypeptide as defined in .7. A vector comprising the nucleic acid molecule as defined in .8. A cell comprising the vector as claimed in .9. A binding moiety capable of specifically binding the polypeptide of .10. The binding moiety of claim 9 , capable of specifically binding the polypeptide when it is in complex with WIC.11. The binding moiety of claim 10 , wherein the binding moiety is a T cell receptor (TCR) or an antibody.12. The binding moiety of claim 11 , wherein the binding moiety is a TCR.13. A method of treating or preventing a disease in a subject in need thereof claim 9 , comprising administering to the subject a therapeutically effective amount of a binding moiety as defined in .14. The ...

BREAST AND OVARIAN CANCER VACCINES

The compositions described herein include an epitope of a peptide that may elicit an immune response in a subject following administration. The compositions may comprise nucleic acids. The compositions may comprise peptides. The methods described herein include administering a composition comprising an epitope of a peptide to a subject in need thereof. 1223-. (canceled)224. A composition comprising an isolated and purified plasmid comprising a nucleotide sequence encoding a plurality of epitopes , wherein the epitopes comprise an amino acid sequence having at least 90% sequence identity to a HER2 amino acid sequence of SEQ ID NO: 60 , SEQ ID NO: 61 , and/or SEQ ID NO: 62 , and/or to one or more IGFBP-2 amino acid sequences selected from SEQ ID NOs: 46-56.225. The composition of claim 224 , wherein the HER2 amino acid sequence has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 60 claim 224 , SEQ ID NO: 61 claim 224 , or SEQ ID NO: 62.226. The composition of claim 224 , wherein the HER2 amino acid sequence has at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 60 claim 224 , SEQ ID NO: 61 claim 224 , or SEQ ID NO: 62.227. The composition of claim 224 , wherein the HER2 amino acid sequence consists of the amino acid sequence of SEQ ID NO: 60 claim 224 , SEQ ID NO: 61 claim 224 , or SEQ ID NO: 62.228. The composition of claim 224 , wherein the nucleotide sequence comprises a nucleotide sequence having at least 95% sequence identity with one or more sequences selected from SEQ ID NO: 57-59.229. The composition of claim 224 , wherein the IGFBP-2 has at least 95% sequence identity to an amino acid sequence selected from SEQ ID NOs: 46-56.230. The composition of claim 229 , wherein the nucleotide sequence comprises a nucleic acid sequence selected from SEQ ID NO: 43-45.231. The composition of claim 224 , wherein the plurality of epitopes further comprises IGF-1R.232. The composition of claim 231 , wherein the IGF-1R comprises an ...

Chimeric chlorotoxin receptors

The invention provides chimeric antigen receptor(s) (CAR(s)) that comprise a fusion protein of CTX or any functional variant thereof or a CTX-like peptide or any functional variant thereof as the extracellular antigen recognition moiety of the CAR. CAR(s) comprising CTX, a CTX-like peptide or functional variants of the foregoing are collectively referred to herein as “CTX-CAR(s).” Such CTX-CAR(s) may further comprise additional moieties or domains in the extracellular domain, a transmembrane domain and at least one intracellular! signaling domain. Such CTX-CAR(s) may be expressed in a host cell, such as, but not limited to, an immune effector cell. The present invention also provides methods of treatment (such as, for example, methods for treating cancer) by providing to the patient in need thereof immune effector cells that are engineered to express a CTX-CAR described herein.

TLX AND MIR-219 AS POTENTIAL THERAPEUTIC TARGETS FOR NEURODEVELOPMENTAL DISORDERS

Disclosed herein are methods of treating neurodevelopmental disorders such as schizophrenia (SCZ), bipolar disorder or depression. The methods entail inhibiting expression of miR-219 or overexpressing TLX thereby promoting proliferation of neural stem cells (NSCs) in the subjects. 1. A method of correcting a defective rate of proliferation in a population of neural stem cells (NSCs) comprising:contacting the population of NSCs with an effective amount of an miR-219 inhibitor, wherein the miR-219 inhibitor causes an increase in NSC proliferation rate.2. The method of claim 1 , wherein contact of the population of NSCs with the miR-219 inhibitor takes place in vitro.3. The method of claim 2 , wherein the population of NSCs is derived from a subject suffering from schizophrenia claim 2 , bipolar disorder claim 2 , or depression.4. The method of claim 1 , wherein contact of the population of NSCs with the miR-219 inhibitor takes place in vivo.5. The method of claim 4 , wherein the population of NSCs is present in the nervous system of a subject suffering from schizophrenia claim 4 , bipolar disorder claim 4 , or depression.6. The method of claim 5 , wherein the increase in NSC proliferation rate maintains normal NSC proliferation of the subject.7. The method of claim 1 , wherein the miR-219 inhibitor is a tough decoy RNA claim 1 , an RNAi molecule claim 1 , or an aptamer.8. The method of claim 7 , wherein the miR-219 inhibitor is an miR-219-5p hairpin inhibitor or TuD-miR-219.9. The method of claim 1 , further comprising contacting the population of NSCs with an effective amount of an agent to increase expression or activity of TLX.10. The method of claim 9 , wherein the agent is a vector expressing a gene encoding TLX.11. A method of correcting a defective rate of proliferation in a population of neural stem cells (NSCs) comprising:contacting the population of NSCs with an effective amount of an agent to increase expression or activity of TLX, wherein the agent causes ...

Fusion proteins for promoting an immune response, nucleic acids encoding same, and methods of making and use thereof

Disclosed herein are compositions, cells, kits, and methods for inducing an immune response in a subject. The compositions can be used as vaccines or vaccine adjuvants against cancer (e.g., melanoma, glioma, prostate, breast) and infectious diseases (e.g., therapeutic and preventative vaccination for viruses), and can be used in cell-based therapies for preventing and treating disorders such as cancer and infection. The compositions, cells, kits and methods involve one or more nucleic acids that encode one or more LMPI fusion proteins (chimeric proteins), and in a typical embodiment, synergistic activation of immune responses by a combination of two or more LMPI fusion proteins.

IL-31 Improves Efficacy of Macrophage-Based Adoptive Cell Therapy for Cancer

The present invention provides macrophages genetically modified to express IL-31 or both IL-31 and a chimeric antigen receptor (CAR) for treatment of cancer. It further provides methods for treatment of cancer comprising administration of IL-31 along with genetically unmodified macrophages or genetically modified to express a CAR. 1. Macrophages which are genetically modified to express (i) human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1; or (ii) a fused protein comprising human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1 , wherein in the fused protein the human IL-31 or peptide is attached to an immunoglobulin amino acid sequence comprising IgG.2. The macrophages according to claim 1 , which are genetically modified to express human IL-31.3. Method of preparing genetically-modified macrophages according to claim 1 , comprising introducing a nucleic acid sequence encoding human IL-31 claim 1 , a peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1 claim 1 , or the fused protein wherein the IL-31 or the peptide is attached to an immunoglobulin amino acid sequence comprising IgG claim 1 , into a population of cells selected from monocytes claim 1 , naïve macrophages or anti-tumor macrophages by transduction methods.4. The method according to claim 3 , of preparing the macrophages genetically modified to express human IL-31 wherein the nucleic acid sequence encoding human IL-31 is introduced into the cells by lentiviral transduction.5. Pharmaceutical composition comprising genetically-modified macrophages according to claim 1 , and a pharmaceutically acceptable carrier.6. The pharmaceutical composition according to claim 5 , wherein the macrophages are genetically modified to express human IL-31.7. Method for ...

Method for Treating Ischemic Tissue

The invention provides a method of increasing blood flow or perfusion in an ischemic tissue; inducing angiogenesis, neovascularization or revascularization; increasing skeletal muscle viability; promoting ischemic skin wound healing; treating or preventing gangrene; and/or treating CLI. In various aspects, the method comprises administering to a subject a hybrid adenoassociated virus (AAV) comprising a nucleotide sequence encoding an E-selectin, AAV serotype 2 (AAV2) inverted terminal repeats (ITRs), and a capsid from an AAV other than serotype 2. In various aspects, the method comprises administering to the subject a cell comprising an AAV comprising a nucleotide sequence encoding an E-selectin, AAV2 ITRs, and a AAV2 capsid. 1. A method of increasing blood flow or perfusion in an ischemic tissue in a subject , comprising administering to the subject in an amount effective to increase the blood flow or perfusion in the ischemic tissue a hybrid adenoassociated virus (AAV) comprising a nucleotide sequence encoding an E-selectin , AAV serotype 2 (AAV2) inverted terminal repeats (ITRs) , and a capsid from an AAV other than serotype 2.2. A method of inducing angiogenesis , neovascularization or revascularization in an ischemic tissue in a subject , comprising administering to the subject in an amount effective to induce angiogenesis , neovascularization or revascularization in the ischemic tissue a hybrid adenoassociated virus (AAV) comprising a nucleotide sequence encoding an E-selectin , AAV serotype 2 (AAV2) inverted terminal repeats (ITRs) , and a capsid from an AAV other than serotype 2.3. A method of increasing skeletal muscle viability in a subject , comprising administering to the subject in an amount effective to increase the skeletal muscle viability a hybrid adenoassociated virus (AAV) comprising a nucleotide sequence encoding an E-selectin , AAV serotype 2 (AAV2) inverted terminal repeats (ITRs) , and a capsid from an AAV other than serotype 2.4. A method of ...

Novel Substitution Mutant Receptors and Their Use in a Nuclear Receptor-Based Inducible Gene Expression System

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel nuclear receptors comprising a substitution mutation and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene within a host cell using this inducible gene expression system. 2. A gene expression modulation system comprising: i) a DNA-binding domain that recognizes a response element associated with a gene whose expression is to be modulated; and', 'ii) a nuclear receptor ligand binding domain; and, 'a) a first gene expression cassette that is capable of being expressed in a host cell comprising a polynucleotide that encodes a first polypeptide comprising i) a transactivation domain; and', 'ii) a nuclear receptor ligand binding domain, 'b) a second gene expression cassette that is capable of being expressed in the host cell comprising a polynucleotide that encodes a second polypeptide comprisingwherein one of the nuclear receptor ligand binding domains is a Group B nuclear receptor ligand binding domain comprising a substitution mutation.3. The gene expression modulation system according to claim 1 , wherein the Group B nuclear receptor ligand binding domain is selected from the group consisting of a retinoid X receptor claim 1 , an H-2 region II binding protein (H-2REIBP) claim 1 , a Nuclear Receptor co-regulator-1 (RCoR-1) claim 1 , an ultraspiracle protein claim 1 , a 2C1 nuclear receptor claim 1 , and a chorion factor 1 (CF-1).4. The gene expression modulation system according to claim 3 , wherein the Group B nuclear receptor ligand binding domain is encoded by a polynucleotide comprising a codon mutation that results in a substitution of an amino acid residue claim 3 , wherein the amino acid residue is at a position equivalent to or analogous to a) 401 or 429 of SEQ TD NO: 1 claim 3 , b) 401 and 429 ...

PROTEIN M FUSION PROTEINS AND USES

Fusion proteins with immunoglobulin binding properties, their uses and related methods and compositions are disclosed. The fusion proteins are comprised of an antibody-binding fragment of protein M from spp. conjugated to a receptor fragment. The receptor fragment is a protein fragment to which a pathogen or a toxin can specifically bind. The fusion proteins can be used to neutralize or eradicate a wide group of pathogens or toxins. 1. A method for neutralizing a pathogen , wherein the pathogen has a specific binding affinity for a receptor fragment , the method comprising: providing conditions for interaction between the pathogen and a fusion protein that comprises a polypeptide having at least 90% identity over its entire length with either the sequence set forth in SEQ ID NO: 1 or the sequence set forth in SEQ ID NO: 2 conjugated to the receptor fragment , whereby the fusion protein binds to and neutralizes the pathogen.2. The method according to claim 1 , wherein the receptor fragment is a protein fragment of a cellular receptor.3. The method according to claim 2 , wherein the pathogen is SARS-CoV-2 virus and the receptor fragment comprises the sequence set forth in SEQ ID NO: 15.4. The method according to claim 1 , wherein the fusion protein further comprises a spacer between the polypeptide and the receptor fragment.5. The method according to claim 1 , wherein the receptor fragment comprises one of the following sequences: SEQ ID NO: 16-36.6. The method according to claim 1 , wherein the fusion protein neutralizes the pathogen via recruitment of C1q protein.7. A method for eradicating a bloodborne pathogen in a subject claim 1 , wherein the pathogen has a specific binding affinity for a receptor fragment inside a body of the subject claim 1 , the method comprising:receiving a sample of blood, serum or plasma from the subject or from a donor compatible with the subject, wherein the sample comprises immunoglobulins;adding a fusion protein that comprises a ...

Flt3l-based chimeric proteins

The present invention relates, inter alia, to compositions and methods, including chimeric proteins comprising an extracellular domain of FMS like tyrosine kinase 3 ligand (FLT3L) and an extracellular domain of a Type II transmembrane protein that find use in the treatment of disease, such as cancer.

MULTIPARTITE SIGNALING PROTEINS AND USES THEREOF

The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease. 1. A non-natural cell , comprising:(a) a first nucleic acid molecule encoding a first fusion protein comprising a first multimerization domain, a hydrophobic domain, and an actuator domain, wherein the first multimerization domain localizes extracellularly when the first fusion protein is expressed; and(b) a second nucleic acid molecule encoding a second fusion protein comprising a binding domain and a second multimerization domain, wherein the second fusion protein localizes extracellularly when expressed;wherein a first bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second fusion proteins.2. The non-natural cell according to claim 1 , wherein the first and second multimerization domains are the same or different.3. The non-natural cell according to or claim 1 , wherein the multimerization domains of the first and second fusion proteins associate with a bridging factor selected from rapamycin or a rapalog thereof claim 1 , coumermycin or a derivative thereof claim 1 , gibberellin or a derivative thereof claim 1 , abscisic acid (ABA) or a derivative thereof claim 1 , methotrexate or a derivative thereof claim 1 , cyclosporin A or a derivative thereof claim 1 , FKCsA or a derivative thereof claim 1 , trimethoprim (Tmp)-synthetic ligand for FKBP (SLF) or a derivative thereof claim 1 , or any combination thereof.4. The non-natural cell according to any one of the preceding claims claim 1 , wherein the first and second multimerization domains are a pair selected from FKBP and FRB claim 1 , FKBP and calcineurin claim 1 , FKBP and cyclophilin claim 1 , FKBP and bacterial DHFR claim 1 ...

MULTIPARTITE SIGNALING PROTEINS AND USES THEREOF

The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease. 1158.-. (canceled)159. A fusion polypeptide comprising from 5′ to 3′:(a) a first polypeptide comprising a first secretion signal, a first multimerization domain, a first transmembrane domain, and an actuator domain;(b) a viral self-cleaving polypeptide; and(c) a second polypeptide comprising a second secretion signal; a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand; a second multimerization domain; and a second transmembrane domain.160. The fusion polypeptide of claim 159 , wherein the viral self-cleaving polypeptide comprises a viral 2A sequence.161. The fusion polypeptide of claim 159 , wherein the viral 2A polypeptide is an aphthovirus 2A peptide claim 159 , a potyvirus 2A peptide claim 159 , or a cardiovirus 2A peptide.162. The fusion polypeptide of claim 159 , wherein the viral 2A polypeptide is selected from the group consisting of: a foot-and-mouth disease virus (FMDV) 2A peptide claim 159 , an equine rhinitis A virus (ERAV) 2A peptide claim 159 , a Thosea asigna virus (TaV) 2A peptide claim 159 , a porcine teschovirus-1 (PTV-1) 2A peptide claim 159 , a Theilovirus 2A peptide claim 159 , and an encephalomyocarditis virus 2A peptide.163. The fusion polypeptide of claim 159 , wherein the first and second secretion signals are the same or different.164. The fusion polypeptide of claim 159 , wherein the first and second multimerization domains are the same or different.165. The fusion polypeptide of claim 159 , wherein the multimerization domains of the first and second polypeptides associate with a bridging factor selected from the group consisting of: rapamycin or a rapalog thereof claim 159 , coumermycin or a derivative thereof claim 159 , gibberellin or a derivative thereof claim ...

Pla2r1 as anti-tumoral compound and as biomarker for the detection of cancer

Compositions comprising a polynucleotide of human PLA2R1, a polypeptide of human PLA2R1 or an extracellular fragment of human PLA2R1 for use in the treatment of cancer in particular breast cancer, pancreatic cancer, colorectal cancer, kidney cancer and melanoma.

METHOD AND COMPOSITION FOR PREDICTING LONG-TERM SURVIVAL IN CANCER IMMUNOTHERAPY

Provided is a peripheral blood biomarker for predicting the long-term survival/need for therapeutic intervention in cancer immunotherapy. The present invention provides a method that uses a composition of a cell subpopulation in a sample obtained from a subject as an indicator to predict the long-term survival of the subject in cancer immunotherapy. The long-term survival/need for therapeutic intervention in a subject in cancer immunotherapy can be predicted by comparing the level of a CD4+ T cell subpopulation that correlates with dendritic cell stimulation in an antitumor immune response or a dendritic cell subpopulation that correlates with dendritic cell stimulation in an antitumor immune response with a reference standard. 1. A method of using a composition of a cell subpopulation in a sample obtained from a subject as an indicator for predicting long-term survival in cancer immunotherapy in the subject , comprising:a step of analyzing the composition of the cell subpopulation in the sample obtained from the subject;{'sup': '+', 'wherein long-term survival in cancer immunotherapy in the subject is predicted by comparing an amount of a CD4 T cell subpopulation correlated with dendritic cell stimulation in an antitumor immune response in the sample with a baseline.'}2. A method of using a composition of a cell subpopulation in a sample obtained from a subject as an indicator for predicting long-term survival in cancer immunotherapy in the subject , comprising:a step of analyzing the composition of the cell subpopulation in the sample obtained from the subject;wherein long-term survival in cancer immunotherapy in the subject is predicted by comparing an amount of a dendritic cell subpopulation correlated with dendritic cell stimulation in an antitumor immune response in the sample with a baseline.3. A method of using a composition of a cell subpopulation in a sample obtained from a subject as an indicator for predicting long-term survival in cancer immunotherapy ...

NOVEL AND POWERFUL MHC-CLASS II PEPTIDES DERIVED FROM SURVIVIN

The present invention relates to peptides, nucleic acids, and cells for use in the immunotherapy of cancer. The present invention furthermore relates to survivin-derived tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention specifically relates to three novel peptide sequences and variants thereof derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses. 1. A pharmaceutical composition comprising a peptide consisting of the amino acid sequence selected from SEQ ID NO: 1 or SEQ ID NO: 2 and an adjuvant.2. The pharmaceutical composition according to claim 1 , wherein the adjuvant is selected from imiquimod claim 1 , resiquimod claim 1 , GM-CSF claim 1 , cyclophosphamide claim 1 , sunitinib claim 1 , bevacizumab claim 1 , interferon-alpha claim 1 , interferon-beta claim 1 , CpG oligonucleotides and derivatives claim 1 , poly-(I:C) and derivatives claim 1 , RNA claim 1 , sildenafil claim 1 , particulate formulations with poly(lactide co-glycolide) (PLG) claim 1 , virosomes claim 1 , interleukin (IL)-1 claim 1 , IL-2 claim 1 , IL-4 claim 1 , IL-7 claim 1 , IL-12 claim 1 , IL-13 claim 1 , IL-15 claim 1 , IL-21 claim 1 , and IL-23.3. The pharmaceutical composition according to claim 1 , wherein the adjuvant comprises IL-2.4. The pharmaceutical composition according to claim 1 , wherein the adjuvant comprises IL-7.5. The pharmaceutical composition according to claim 1 , wherein the adjuvant comprises IL-15.6. The pharmaceutical composition according to claim 1 , wherein the adjuvant comprises IL-21.7. The pharmaceutical composition according to claim 1 , further comprising a pharmaceutically acceptable liquid.8. The pharmaceutical composition of claim 1 , wherein the peptide ...

COMPOSITIONS AND METHODS OF PHOSPHOLIPASE A2 RECEPTOR CHIMERIC AUTOANTIBODY RECEPTOR T CELLS

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an anti-phospholipase A2 receptor (PLA2R) autoantibody-based B cell receptor, polynucleotides encoding the CAAR, vectors comprising a polynucleotide encoding the CAAR, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified cell, e.g., a genetically modified T cell, expressing a PLA2R-CAAR wherein the expressed CAAR comprises a PLA2R extracellular domain. 169.-. (canceled)70. A polynucleotide encoding a chimeric autoantibody receptor (CAAR) , wherein the CAAR comprises:(i) an extracellular domain comprising a phospholipase A2 receptor (PLA2R) autoantigen or fragment thereof comprising a cysteine rich domain, a C-type lectin domain 1, and a C-type lectin domain 7;(ii) a transmembrane domain;(iii) an intracellular domain of a costimulatory molecule; and(iv) a signaling domain.71. The polynucleotide of claim 70 , wherein the PLA2R autoantigen or fragment thereof further comprises a fibronectin type II domain claim 70 , a C-type lectin domain 2 claim 70 , a C-type lectin domain 3 claim 70 , or any combination thereof.72. The polynucleotide of claim 70 , wherein the PLA2R autoantigen or fragment thereof comprises:(a) a cysteine rich domain, a fibronectin type II domain, a C-type lectin domain 1, a C-type lectin domain 2, a C-type lectin domain 3, and a C-type lectin domain 7; or(b) a cysteine rich domain, a fibronectin type II domain, a C-type lectin domain 1, and a C-type lectin domain 7.73. The polynucleotide of claim 70 , wherein the PLA2R autoantigen or fragment thereof comprises the amino acid sequence of SEQ ID NO: 55 claim 70 , the amino acid sequence of SEQ ID NO: 57 claim 70 , or the amino acid sequence of SEQ ID NO: 59.74. The polynucleotide of claim 70 , wherein the transmembrane domain comprises a CD8 alpha chain transmembrane domain.75. The polynucleotide of claim 74 , wherein the CD8 alpha ...

Treatment of cancer using a cd33 chimeric antigen receptor

The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.

Novel Ecdysone Receptor/Invertebrate Retinoid X Receptor-Based Inducible Gene Expression System

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/invertebrate retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms. 1. A gene expression modulation system comprising: i) a DNA-binding domain that recognizes a response element associated with a gene whose expression is to be modulated; and', 'ii) an ecdysone receptor ligand binding domain; and, 'a) a first gene expression cassette that is capable of being expressed in a host cell comprising a polynucleotide that encodes a first hybrid polypeptide comprising 'i) a transactivation domain; and ii) an invertebrate retinoid X receptor ligand binding domain.', 'b) a second gene expression cassette that is capable of being expressed in the host cell comprising a polynucleotide that encodes a second hybrid polypeptide comprising2. The gene expression modulation system according to claim 1 , further comprising a third gene expression cassette comprising:i) a response element recognized by the DNA-binding domain of the first hybrid polypeptide binds;ii) a promoter that is activated by the transactivation domain of the second hybrid polypeptide; and iii) a gene whose expression is to be modulated.3Choristoneura fumiferanaTenebrio molitorManduca sextaHeliothies virescensChironomus tentansBombyx moriDrosophila melanogasterAedes aegyptiLucilia capitataLucilia cuprinaCeratitis capitataLocusta migratoriaMyzus persicaeCeluca pugilatorAmblyomma americanumBamecia argentifoliNephotetix cincticeps. The gene expression modulation system according to claim 1 , wherein the ecdysone receptor ligand binding domain ...

Chimeric Retinoid X Receptors and Their Use in a Novel Ecdysone Receptor-Based Inducible Gene Expression System

This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/chimeric retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms. 135.-. (canceled)36. An isolated polynucleotide selected from the group consisting of:(a) a polynucleotide encoding a truncated chimeric retinoid X receptor ligand binding domain comprising a truncation mutation, wherein the truncation mutation reduces ligand binding activity of the truncated chimeric retinoid X receptor ligand binding domain;(b) a polynucleotide encoding a truncated chimeric retinoid X receptor ligand binding domain comprising a truncation mutation, wherein the truncation mutation reduces steroid binding activity of the truncated chimeric retinoid X receptor ligand binding domain;(c) a polynucleotide encoding a truncated chimeric retinoid X receptor ligand binding domain comprising a truncation mutation, wherein the truncation mutation reduces non-steroid binding activity of the truncated chimeric retinoid X receptor ligand binding domain;(d) a polynucleotide encoding a truncated chimeric retinoid X receptor ligand binding domain comprising a truncation mutation, wherein the truncation mutation enhances ligand binding activity of the truncated chimeric retinoid X receptor ligand binding domain;(e) a polynucleotide encoding a truncated chimeric retinoid X receptor ligand binding domain comprising a truncation mutation, wherein the truncation mutation enhances steroid binding activity of the truncated chimeric retinoid X receptor ligand binding domain;(f) a polynucleotide encoding a truncated chimeric retinoid X ...

QUADRICISTRONIC SYSTEM COMPRISING A HOMING RECEPTOR AND CHIMERIC ANTIGEN RECEPTOR FOR STABLE GENETIC MODIFICATION OF CELLULAR IMMUNOTHERAPIES

Provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) a homing receptor, ii) Antigen Binding Protein (ABP) or Chimeric Antigen Receptor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Further provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) IL-12 and/or TGF-beta trap, ii) an Antigen Binding Protein (ABP) or Chimeric Antigen Receptor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Also provided are compositions and kits comprising the modified NK-92® cells, as well as methods of treating cancer using the modified cells. 1. A method of treating a cancer or reducing cancer metastasis in a subject , the method comprising administering to the subject a therapeutically effective amount of the modified NK-92 cells ,wherein the modified NK-92 cells comprise a nucleic acid encoding IL-12 and/or a TGF-beta trap operably linked to a promoter, andwherein administration treats the cancer, or reduces cancer metastasis in the subject.2. The method of claim 1 , wherein from 1×10to 1×10 claim 1 , per mof the NK-92 cells are administered to the subject.3. The method of claim 1 , wherein the NK-92 cells are administered parenterally claim 1 , intravenously claim 1 , peritumorally claim 1 , intratumorally claim 1 , or by infusion. The present application is a divisional of U.S. patent application Ser. No. 16/529,029 filed Aug. 1, 2019, which claims the benefit of priority to U.S. provisional applications with the Ser. Nos. 62/713,264, filed Aug. 1, 2018; 62/713,278, filed Aug. 1, 2018, 62/713,310 filed Aug. 1, 2018; and 62/713,323 filed on Aug. 1, 2018. Each of these applications is incorporated by reference herein in its entirety. ...

METHYL DEGRON PEPTIDE AND METHODS OF CONTROLLING PROTEIN LIFESPAN

The present invention provides an isolated methyl degron peptide and a fusion protein comprising a methyl degron peptide. Also, the present invention provides screening methods for agents affecting protein lifespan and anti-cancer agents. Moreover, the present invention provides methods of controlling protein lifespan, regulating protein expression, and treating cancers by using a methyl degron peptide or a methyl degron gene. 1. An isolated methyl degron peptide.2. The isolated methyl degron peptide of claim 1 , wherein the peptide is methylated by Enhancer of Zeste Homolog 2 lysine methyltransferse (EZH2).3. The isolated methyl degron peptide of claim 1 , wherein the peptide is recognized by DDB1-CUL4-associated factor 1 adaptor (DCAF1).4. The isolated methyl degron peptide of claim 1 , wherein the peptide is involved in ubiquitin-dependent protein degradation.5. The isolated methyl degron peptide of claim 1 , wherein the peptide is SEQ ID NO: 1.6. A fusion protein comprising the methyl degron peptide of .7. The fusion protein of claim 6 , wherein the protein has reduced lifespan.8. The fusion protein of claim 7 , wherein the fusion protein has a carcinogenic effect.9. A protein having an extended lifespan obtained by mutation of the methyl degron peptide of .10. The protein of claim 9 , wherein the protein has an anticancer effect due to its extended lifespan.11. A method of regulating protein lifespan claim 5 , comprising utilizing the methyl degron peptide of .12. A method for screening an agent that controls protein lifespan claim 5 , the method comprising:(a) culturing a cell;(b) treating the cell with a potential agent;(c) analyzing the methylation level of a methyl degron peptide in the cell; and(d) determining the potential agent to be an agent that reduces protein lifespan, when the methylation level is increased, and determining the potential agent to be an agent that increases protein lifespan, when the methylation level is decreased.13. A method for ...

GAL-1 Variants Having Immuno-Modulating Properties and Methods of Using the Same

Galectin-1 polypeptide variants that include a mutation of the histidine residue corresponding to position 52 of the full-length amino acid sequence of native human Gal-1 as shown in SEQ ID NO: 1, the mutation being a substitution of the histidine to tyrosine or asparagine, providing resistance to acidosis otherwise resulting in deactivation of the native human Gal-1. The Galectin-1 polypeptide variants may include one or more additional mutation(s) of the cysteine residue corresponding to a position selected from 2, 16, 88, or combinations thereof of the full-length amino acid sequence of native human Gal-1 as shown in SEQ ID NO: 1, the additional mutation being a substitution of the cysteine to serine, and providing resistance to oxidation. 1. A Gal-1 polypeptide variant , comprising:a mutation of the histidine residue corresponding to position 52 of the full-length amino acid sequence of native human Gal-1 as shown in SEQ ID NO: 1, the mutation being a substitution of the histidine to tyrosine or asparagine,wherein the Gal-1 polypeptide variant is resistant to acidic conditions of an inflammatory microenvironment that otherwise result in deactivation of native human Gal-1.2. A nucleic acid encoding a Gal-1 polypeptide variant having a mutation of the histidine residue corresponding to position 52 of the full-length amino acid sequence of native human Gal-1 as shown in SEQ ID NO: 1 , the mutation being a substitution of the histidine to tyrosine or asparagine ,wherein the Gal-1 polypeptide variant is resistant to acidic conditions of an inflammatory microenvironment that otherwise result in deactivation of native human Gal-1.3. A pharmaceutical composition , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the Gal-1 polypeptide variant of , or a fragment thereof; and'}a pharmaceutically acceptable carrier.4. The Gal-1 polypeptide variant of claim 1 , further comprising a mutation of the cysteine residue corresponding to a position selected from 2 ...

QUADRICISTRONIC SYSTEM COMPRISING A HOMING RECEPTOR AND CHIMERIC ANTIGEN RECEPTOR FOR STABLE GENETIC MODIFICATION OF CELLULAR IMMUNOTHERAPIES

Provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) a homing receptor, ii) Antigen Binding Protein (ABP) or Chimeric Antigen Receptor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Further provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) IL-12 and/or TGF-beta trap, ii) an Antigen Binding Protein (ABP) or Chimeric Antigen Receptor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Also provided are compositions and kits comprising the modified NK-92® cells, as well as methods of treating cancer using the modified cells. 1. A modified NK-92 cell comprising a nucleic acid encoding a homing receptor operably linked to a promoter.2. The modified NK-92 cell of claim 1 , wherein the homing receptor is a chemokine receptor selected from CCR7 claim 1 , CCL19 claim 1 , CCL21 claim 1 , CXCR2 claim 1 , IL-8 claim 1 , CXCL1 claim 1 , or the receptor for CXCL14 claim 1 , and the cell adhesion molecules is selected from L-selectin (CD62L) claim 1 , α4β7 integrin claim 1 , LPAM-1 claim 1 , and LFA-1.3. The modified NK-92 cell of claim 2 , wherein the nucleic acid encoding CCR7 has at least 90% claim 2 , 91% claim 2 , 92% claim 2 , 93% claim 2 , 94% claim 2 , 95% claim 2 , 96% claim 2 , 97% claim 2 , 98% or 99% identity to SEQ ID NO:1.4. The modified NK-92 cell of claim 1 , wherein the modified NK-92 cell further comprises a nucleic acid encoding an antigen binding protein operably linked to a promoter claim 1 , and wherein the antigen binding protein specifically binds a tumor associated antigen.5. The modified NK-92 cell of claim 4 , wherein the tumor associated antigen is selected from CD19 claim 4 , CD20 claim 4 , NKG2D ...

CHIMERIC RECEPTOR WITH NKG2D SPECIFICITY FOR USE IN CELL THERAPY AGAINST CANCER AND INFECTIOUS DISEASE

The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompansses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases. 137-. (canceled)38. A method of producing an expanded population of natural killer (NK) cells , said method comprising:obtaining a peripheral blood sample,isolating from said peripheral blood sample a mixed population of mononuclear cells comprising NK cells and T cells,culturing said mixed population of cells under culture conditions resulting in the enhanced expansion of NK cells as compared to T cells,depleting the mixed population of residual T cells, andintroducing into the NK cells nucleic acid encoding a chimeric receptor, the chimeric receptor comprising:i) an extracellular receptor domain, wherein said extracellular receptor domain comprises a peptide that binds one or more native ligands of Natural Killer Group 2 member D (NKG2D) receptor, andii) one or more peptides that recruit downstream signaling effector molecules in response to binding of a native ligand by said extracellular receptor domain.39. The method of claim 38 , wherein the culture conditions comprise culturing said mixed population of mononuclear cells with K562 myeloid leukemia cells claim 38 , wherein said K562 myeloid leukemia cells are genetically modified to express membrane bound interleukin-15 and 4-1BB ligand claim 38 , wherein the extracellular receptor domain is encoded by a first polypeptide that also encodes a CD3zeta signaling domain claim 38 , and wherein the extracellular receptor domain binds the native ligand of NKG2D.40. The method of claim 38 , wherein said T cells are removed using beads coupled to an anti-CD3 antibody.41. The ...

ADENO-ASSOCIATED VIRUS VECTOR MEDIATED GENE THERAPY FOR OPHTHALMIC DISEASES

The present invention provides compositions and methods for treating an ocular condition and/or disease. In particular, compositions and methods of the invention are directed to a gene therapy for treatment of an ocular condition and/or disease. One particular aspect of the invention provides a recombinant DNA comprising (i) a therapeutic gene, a functional counterpart of a defective gene associated with manifestation said ocular condition or disease, or a combination thereof; and (ii) a delivery vehicle adapted for delivering said gene of (i) to cells in target ocular area for treating said ocular condition or disease, said delivery vehicle comprising an adeno-associated virus (AAV) serotype. 2. The recombinant DNA of claim 1 , wherein said therapeutic gene is selected from the group consisting of:(a) human nuclear hormone receptor (hNHR) gene or a fragment thereof, wherein said hNHR gene is selected from the group consisting of NR2E3, NR1C3, NR1D1, RORA, NUPR1, NR2C1, and LXRa; (i) anti-vegf:', '(ii) lens epithelium derived growth factor;', '(iii) tumstatin;', '(iv) transferrin and tumstatin fusion protein;', '(v) fibroblast growth factor;', '(vi) platelet-derived growth factor family;', '(vii) vascular endothelial growth factor sub-family;', '(viii) epidermal growth factor family;', '(ix) fibroblast growth factor family;', '(x) transforming growth factor-0 superfamily;', '(xi) angiopoietin-like family;', '(xii) galectins family;', '(xiii) integrin superfamily;', '(xiv) hepatocyte growth factor;', '(xv) angiopoietins;', '(xvi) endothelins;', '(xvii) hypoxia-inducible factors;', '(xviii) insulin-like growth factors;', '(xix) cytokines; and', '(xx) matrix metalloproteinases gene or a fragment thereof; and, '(b) a growth factor or an angiogenic modulator gene that encodes a peptide selected from the group consisting of(c) a combination thereof.3. The recombinant DNA of claim 1 , wherein said delivery vehicle comprises adeno-associate virus (AAV) inverted terminal ...

CHIMERIC ANTIGEN AND T CELL RECEPTORS AND METHODS OF USE

The invention provides a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising extracellular domain disclosed herein. Some aspects of the invention relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising the extracellular domain disclosed herein. Other aspects of the invention relate to cells comprising the CAR or the TCR and their use in a T cell therapy. 133-. (canceled)34. A method of inducing immunity against a tumor in a subject in need thereof , comprising administering to the subject an effective amount of a cell comprising a polynucleotide encoding a chimeric antigen receptor (CAR) , of a vector comprising the polynucleotide , of a polypeptide encoded by the polynucleotide , or of any combination thereof , wherein the CAR comprises:(i) an antigen binding molecule;(ii) a costimulatory domain, consisting of SEQ ID NO: 241; and(iii) an intracellular activation domain from CD3 zeta;wherein the antigen binding molecule is linked to the costimulatory domain through 1 to 6 heterologous amino acids; andwherein the antigen is selected from ErbB2 (HER2/neu), carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), EGFR variant III (EGFRvIII), CD19, CD20, CD30, CD40, disialoganglioside GD2, ductal-epithelial mucine, gp36, TAG-72, glycosphingolipids, glioma-associated antigen, B-human chorionic gonadotropin, alphafetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RU1, RU2 (AS), intestinal carboxyl esterase, mut hsp70-2, M-CSF, prostase, prostase specific antigen (PSA), PAP, NY-ESO-1, LAGA-1a, p53, mutated p53, prostein, PSMA, survivin and telomerase, prostate-carcinoma tumor antigen-1 (PCTA-1), MAGE, MAGE-A1, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin growth factor (IGFI)-I, IGF-II, IGFI receptor, a major histocompatibility complex (MHC) molecule presenting a tumor-specific ...

MULTIPARTITE SIGNALING PROTEINS AND USES THEREOF

The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease. 1. An isolated non-natural cell , comprising:(a) a first fusion protein comprising a first multimerization domain, a first transmembrane domain, and an actuator domain, wherein the first multimerization domain localizes extracellularly when the first fusion protein is expressed; and(b) a second fusion protein comprising a secretion signal, a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand, a second multimerization domain, and a second transmembrane domain, wherein the second fusion protein localizes extracellularly when expressed;wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second fusion proteins.2. The isolated non-natural cell of claim 1 , wherein the first and second multimerization domains are the same or different.3. The isolated non-natural cell of claim 1 , wherein the multimerization domains of the first and second fusion proteins associate with a bridging factor selected from the group consisting of: rapamycin or a rapalog thereof claim 1 , coumermycin or a derivative thereof claim 1 , gibberellin or a derivative thereof claim 1 , abscisic acid (ABA) or a derivative thereof claim 1 , methotrexate or a derivative thereof claim 1 , cyclosporin A or a derivative thereof claim 1 , FK506/cyclosporin A (FKCsA) or a derivative thereof claim 1 , and trimethoprim (Tmp)-synthetic ligand for FK506 binding protein (FKBP) (SLF) or a derivative thereof.4. The isolated non-natural cell of claim 1 , wherein the first and second multimerization domains are a pair selected from the group consisting of: FKBP and FKBP12-rapamycin ...

TREATMENT OF CANCER USING A CD33 CHIMERIC ANTIGEN RECEPTOR

The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain. 164-. (canceled)65. A method of providing an anti-tumor immunity in a mammal , comprising administering to the mammal an effective amount of a cell comprising a chimeric antigen receptor (CAR) polypeptide , or a nucleic acid encoding the CAR polypeptide , wherein the CAR polypeptide comprises a CD33 binding domain , a transmembrane domain , and an intracellular signaling domain comprising a costimulatory domain , a primary signaling domain , or both a costimulatory domain and a primary signaling domain , and wherein said CD33 binding domain comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:(i) a heavy chain variable region comprising:a heavy chain complementary determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 274, a heavy chain complementary determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 283, and a heavy chain complementary determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO:292 present in order of HC CDR1, HC CDR2, and HC CDR3; anda light chain variable region comprising:a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 301, a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 310, and a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO:319 present in order of LC CDR1, LC CDR2, and LC CDR3;(ii) a heavy chain variable region comprising:a heavy chain complementarity determining region 1 (HC CDR1) comprising the ...

METHOD FOR PRODUCING ANTIBODY USING "NAKED" EXPRESSION VECTOR EXPRESSING TYPE II TRANSMEMBRANE FUSION PROTEIN

Methods are disclosed for generating antibodies and an expression vector used to express protein(s) which provoke the antibody response. The expression vector may be useful in generating an antibody directed to an antigen, comprising a gene in operable linkage with a promoter, which gene encodes upon expressing a fusion protein comprising (i) CD134L, a fragment, homologous or orthologues protein thereof as N-terminal moiety of the fusion protein; and (ii) all or part of an antigenic protein as C-terminal moiety of the fusion protein. To generate the antibodies, the vector is injected into a subject animal, which produces a fusion protein, against which antibodies are generated. 1. An expression vector for generating an antibody directed to an antigen , the expression vector comprising a polynucleotide in operable linkage with a promoter , wherein the polynucleotide encodes a fusion protein comprising:(i) a polypeptide having at least 35% amino acid identity to the polypeptide of SEQ ID NO:2 which anchors in a cell membrane as the N-terminal moiety of the fusion protein; and(ii) an antigenic protein or an antigenic fragment thereof as the C-terminal moiety of the fusion protein.2. The expression vector of claim 1 , wherein said N-terminal moiety of the fusion protein comprises the polypeptide of SEQ ID NO: 26 or a polypeptide having at least 95% amino acid sequence identity to the polypeptide of SEQ ID NO. 26 which anchors in a cell membrane.3. The expression vector of claim 1 , wherein said N-terminal moiety of the fusion protein comprises the polypeptide of SEQ ID NO: 27 or a polypeptide having at least 95% amino acid sequence identity to the polypeptide of SEQ ID NO. 27 which anchors in a cell membrane.4. The expression vector of claim 1 , wherein said N-terminal moiety of the fusion protein comprises the polypeptide of SEQ ID NO: 28 or a polypeptide having at least 95% amino acid sequence identity to the polypeptide of SEQ ID NO. 28 which anchors in a cell ...

HETERODIMERS AND METHODS OF USE THEREOF

Heterodimers are provided. Accordingly, there is provided a heterodimer comprising a dimerizing moiety attached to at least one amino acid sequence of at least one type I membrane protein capable of at least binding a natural ligand or receptor of said at least one type I membrane protein and to at least one amino acid sequence of at least one type II membrane protein capable of at least binding a natural ligand or receptor of said at least one type II membrane protein. Also provided are nucleic acid constructs and systems encoding the heterodimer, host-cells expressing same and methods of use thereof. 1. A heterodimer comprising a dimerizing moiety attached to at least one amino acid sequence of at least one type I membrane protein capable of at least binding a natural ligand or receptor of said at least one type I membrane protein and to at least one amino acid sequence of at least one type II membrane protein capable of at least binding a natural ligand or receptor of said at least one type II membrane protein.2. The heterodimer of claim 1 , wherein said dimerizing moiety is a proteinaceous moiety.3. The heterodimer of claim 1 , wherein monomers of said heterodimer are not covalently attached.4. The heterodimer of claim 1 , wherein said dimerizing moiety is an Fc domain of an antibody or a fragment thereof.5. The heterodimer of claim 1 , wherein said at least one type I membrane protein is selected from the group consisting of PD1 claim 1 , SIRPα claim 1 , LAG3 claim 1 , BTN3A1 claim 1 , CD27 claim 1 , CD80 claim 1 , CD86 claim 1 , ENG claim 1 , NLGN4X claim 1 , CD84 claim 1 , TIGIT claim 1 , CD40 claim 1 , IL-8 claim 1 , IL-10 claim 1 , CD164 claim 1 , LY6G6F claim 1 , CD28 claim 1 , CTLA4 claim 1 , BTLA claim 1 , LILRB1 claim 1 , LILRB2 claim 1 , TYROBP claim 1 , ICOS claim 1 , VEGFA claim 1 , CSF1 claim 1 , CSF1R claim 1 , VEGFB claim 1 , BMP2 claim 1 , BMP3 claim 1 , GDNF claim 1 , PDGFC claim 1 , PDGFD claim 1 , RAETIE claim 1 , CD155 claim 1 , CD166 claim 1 ...

MODIFIED STEM CELL MEMORY T CELLS, METHODS OF MAKING AND METHODS OF USING SAME

The disclosure provides a method of producing modified stem memory T cells (e.g. CAR-T cells) for administration to a subject as, for example an adoptive cell therapy. 1. (canceled)2. A method of producing a plurality of modified stem memory T cells (T) or modified T-like cells , comprising introducing into a plurality of primary human T cells (a) a transposon composition comprising a transposon comprising an antigen receptor , a therapeutic protein or a sequence encoding the same and (b) a transposase composition comprising a transposase or a sequence encoding the transposase to produce a plurality of modified T cells , under conditions that preserve desirable stem-like properties of the plurality of modified T cells;wherein the conditions comprise culturing the plurality of modified T cells in vitro in a liquid culture media comprising a sterol; an alkane; phosphorus and one or more of an octanoic acid, a palmitic acid, a linoleic acid, and an oleic acid;{'sub': SCM', 'SCM, 'wherein at least 25% of the plurality of modified T cells expresses one or more cell-surface marker(s) of a stem memory T cell (T) or a T-like cell and wherein the one or more cell-surface marker(s) comprises CD62L and CD45RA,'}{'sub': SCM', 'SCM, 'thereby producing a plurality of modified stem memory T cells (T) or modified T-like cells.'}3. The method of claim 2 , wherein at least 60% of the plurality of modified T cells expresses one or more cell-surface marker(s) of a stem memory T cell (T) or a T-like cell.46-. (canceled)7. The method of claim 2 , wherein the transposon is a plasmid DNA transposon with a sequence encoding the antigen receptor or the therapeutic protein flanked by two cis-regulatory insulator elements.8. The method of claim 2 , wherein the transposon is a piggyBac transposon.9. The method of claim 8 , wherein the transposase is a piggyBac transposase.10. The method of claim 9 , wherein the piggyBac transposase comprises an amino acid sequence comprising SEQ ID NO: 4.11. ...

Compositions and methods related to prostate cancer

This disclosure describes markers that can identify patients at risk of developing castration-resistant prostate cancer. The markers, and analyses that use the markers, can be used by health professionals to guide treatment decisions by, for example, helping to evaluate the likelihood that a patient will respond to or develop resistance to prostate cancer therapies targeted to the androgen receptor. Thus, in some cases, methods described herein may be used to identify subjects under treatment for prostate cancer as at risk for developing castration-resistant prostate cancer. Such an evaluation may indicate that a change in prescribed therapy is appropriate. In some of these instances, the change may involve modifying the subject's treatment regimen to include administration of a pharmaceutical composition effective for treating castration-resistant prostate cancer before resistance to androgen receptor-based treatments develops.

MICROBIAL GLYCANS AS A TARGET OF HUMAN INTELECTIN

The present disclosure provides for methods of diagnosing and treating bacterial infections. Human Intelectin 1 (hIntL-1) has been shown to bind selectively to glycan components on bacteria including and . This interaction can be targeted to identify, purify and therapeutically target such organisms. 1. A method for detecting the presence of a microorganism comprising:(i) contacting a sample or an environment suspected of containing the microorganism with a human intelectin molecule, and(ii) detecting binding of the human intelectin molecule to the microorganism.2. The method of wherein the microorganism is a bacterium or a fungus.3Streptococcus pneumonia, Proteus mirabilis, Proteus vulgaris, Klebsiella pneumoniaYersinia pestis.. The method of claim 2 , wherein the bacterium is or4Cryptococcus neoformansAspergillus fumigatus.. The method of claim 2 , wherein the fungus is or5. The method of claim 1 , wherein the microorganism expresses a glycan molecule containing a vicinal 1 claim 1 ,2-diol.6. The method of claim 1 , wherein human intelectin binds to a β-linked D-galactofuranose residue claim 1 , a glycan containing a heptose claim 1 , D-glycero-D-talo-oct-2-ulosonic acid (KO) and/or 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) residue claim 1 , and/or a saccharide residue modified with a phospho-glycerol (Gro-P) substituent.7. The method of claim 1 , wherein the human intelectin claim 1 , or a variant thereof claim 1 , is conjugated to a label or reporter.8. The method of claim 1 , wherein the sample or environment contains human glycans.9. The method of claim 1 , wherein the sample comprises a human tissue or body fluid claim 1 , such as blood or serum.10. The method of claim 1 , wherein the sample comprises a water or waste sample.11. The method of claim 1 , wherein the human intelectin molecule is immobilized on a support.12. The method of claim 11 , wherein the support is a dipstick claim 11 , bead claim 11 , chip claim 11 , microwell claim 11 , filter claim 11 , ...

GENETICALLY MODIFIED NK CELLS AND USES THEREOF

Disclosed herein include a natural killer (NK) cell genetically modified to comprise a recombinant nucleic acid encoding C-X-C Motif Chemokine Receptor 1 (CXCR1), a pharmaceutical composition comprising the NK cell, methods of preparing the NK cell, and method of treating cancer or tumor using the NK cell. 1. A natural killer (NK) cell genetically modified to comprise a recombinant nucleic acid encoding C-X-C Motif Chemokine Receptor 1 (CXCR1).2. The NK cell of claim 1 , further genetically modified to express a recombinant chimeric antigen receptor (CAR) comprising an intracellular signaling domain claim 1 , a transmembrane domain claim 1 , and an extracellular domain comprising an antigen binding region.3. The NK cell of claim 2 , wherein the intracellular signaling domain comprises at least one immunoreceptor tyrosine based activation motif (ITAM)-containing domain.4. The NK cell of claim 2 , wherein the intracellular signaling domain is CD3ζ.5. The NK cell of claim 2 , wherein the transmembrane domain is CD8 transmembrane domain.6. The NK cell of claim 2 , wherein the antigen binding region binds a tumor associated antigen.7. The NK cell of claim 6 , wherein the tumor associated antigen is solid tumor associated antigen.8. The NK cell of claim 2 , wherein the extracellular domain of the recombinant CAR comprises the extracellular domain of an NK cell activating receptor or a scFv fragment of a monoclonal antibody.9. The NK cell of claim 2 , wherein the extracellular domain of the recombinant CAR comprises the extracellular domain of an NKG2D receptor or a scFv fragment of an anti-EPCAM monoclonal antibody.10. The NK cell of claim 2 , wherein the recombinant CAR further comprises claim 2 , between the antigen binding region and the transmembrane region claim 2 , a hinge region.11. The NK cell of claim 10 , wherein the hinge region is a CD8 hinge region.12. A pharmaceutical composition comprising a pharmaceutically effective amount of the NK cell of and a ...

COMPOSITIONS AND METHODS FOR TISSUE REPAIR

The present invention provides compositions and methods for targeting an extracellular matrix derived (EMD) peptide predominantly to an injured tissue, as opposed to an uninjured tissue in vivo. The targeted EMD peptide facilitates the repair and/or regeneration of the injured tissue by providing a surface for cells to attach and grow, thereby facilitating the repair and/or regeneration of the injured tissue. 1. A composition for repair of an injured tissue , the composition comprising an injury-associated antigen-specific binding component conjugated to an extracellular matrix derived (EMD) peptide ,wherein the injury-associated antigen-specific binding component comprising a molecule that specifically binds an antigen expressed following tissue injury, andwherein the EMD peptide is a peptide or a concatamer of a peptide that ranges in length from about 8 amino acid residues to about 100 amino acid residues, and exhibits the ability to: (i) activate cells; (ii) attach cells; and (iii) exhibits a chemotropic property.2. The composition of claim 1 , wherein the EMD peptide further exhibits an angiogenic property.3. The composition of claim 1 , wherein the EMD peptide is a concatamer.4. The composition of claim 1 , wherein the EMD peptide is selected from the group consisting of a Hep III peptide as shown in SEQ ID NO:2 claim 1 , and an RGD peptide as shown in SEQ ID NO:4.5. The composition of claim 1 , wherein the EMD peptide is derived from a protein selected from the group consisting of collagen claim 1 , laminin claim 1 , tenascin-C claim 1 , fibronectin claim 1 , fibrin claim 1 , and elastin.6. The composition of claim 1 , wherein the injury-associated antigen is a member selected from the group consisting of: myosin light chain claim 1 , myosin heavy chain claim 1 , troponin I claim 1 , VCAM-1 claim 1 , ICAM-1 claim 1 , P-selectin claim 1 , E-selectin claim 1 , L-selectin claim 1 , Mo1/CD18 claim 1 , TNF receptor-1 claim 1 , TNF receptor-2 claim 1 , caspase-3 ...

Induced Stem Memory T-Cells and Methods of Use Thereof

Methods and compositions for inducing CD8+ T cells to express a CD62LCD44naïve-like phenotype are provided. One embodiment provides a pharmaceutical composition containing CD8+ T cells induced to express a CD62LCD44naïve-like phenotype and optionally an excipient. The CD8+ T cells can be induced by contacting them with an effective amount of a MEK1/2 inhibitor. An exemplary MEK1/2 inhibitor is Selumetinib. The induced CD8+ cells can be used to treat cancer, reduce tumor burden, or treat infections in a subject in need thereof. 1. A pharmaceutical composition comprising:{'sup': +', 'hi', 'lo, 'a population of CD8 T-cells induced to express CD62LCD44naïve-like phenotype and optionally an excipient.'}2. The composition of claim 1 , wherein the CD8 T-cells are induced to express CD62LCD44naïve-like phenotype by contacting the CD8+ T cells with an effective amount of an inhibitor of MEK1/2.3. The composition of claim 2 , wherein the MEK1/2 inhibitor comprises Selumetinib.4. The pharmaceutical composition of claim 1 , comprising 10to 10induced CD8+ T cells.5. A method for inducing a stem cell memory T cells (T) like phenotype in CD8 T-cells comprising{'sup': +', '+, 'sub': 'SCM', 'contacting the CD8 T-cells in vitro with an effective amount of an inhibitor of MEK1/2 to induce a Tphenotype in the CD8 T-cells; and optionally'}{'sup': '+', 'expanding the induced CD8 T-cells in culture.'}6. The method of claim 5 , wherein the induced CD8 T-cells comprise CD62LCD44naïve-like CD8 T-cells having elevated levels of Sca1 compared to untreated naïve cells.7. The method of claim 5 , wherein the MEK1/2 inhibitor comprises Selumetinib.8. A method for treating an infection or cancer comprising administering the pharmaceutical composition of to a subject in need thereof in combination or alternation with an immunostimulatory agent claim 1 , a potentiating agent claim 1 , or a combination thereof.9. The method of claim 8 , wherein the potentiating agent comprises cyclophosphamide.10. The ...

Molecular system for cancer biology

An engineered dendritic cell including a nanostructure, RNAi based logic circuit, a CRISPR-Cas9 system/light activated CRISPR-Cas9 system (or a modulating CRISPR-Cas9 system) and a sensing protein and/or an activating protein for enhanced interaction with a T-cell and/or a natural killer cell against a particular type of cancer cells is disclosed. The engineered dendritic cell can be ex vivo or in vivo (implanted as a biodegradable/biocompatible lymph node). Furthermore, the CRISPR-Cas9 system can be replaced by Cas9-HFI or Cas12a or a transposon-encoded CRISPR-Cas system. 1. An engineered dendritic cell comprises:(a) a first bioactive molecule;wherein the first bioactive molecule is selected from the group consisting of: a co-stimulating molecule, a mobility enhancing molecule and a programming molecule,(b) an identifying protein on the surface of a cancer cell, or a sensing protein to detect a cancer cell; and(c) a nanostructure,wherein the nanostructure comprises a deoxyribonucleic acid (DNA) origami based nanostructure, or a ribonucleic acid (RNA) origami based nanostructure, or a XNA origami based nanostructure for interaction with a T-cell, and/or a natural killer cell against a cancer cell,wherein XNA comprises genetic bases adenine (A), thymine (T), guanine (G), cytosine (C) and uracil (U), and one or more synthetic or artificial genetic bases,wherein the nanostructure is encapsulated in a lipid bilayer, or the nanostructure is attached with a red blood cell, or a white blood cell.2. The engineered dendritic cell in claim 1 , further comprises a second bioactive molecule to initiate response of the T-cell claim 1 , and/or the natural killer cell.3. The engineered dendritic cell in claim 1 , further comprises an activating protein to detect a molecular event within a cancer cell.4. The engineered dendritic cell in claim 1 , further exchanges or transfers the identifying protein claim 1 , or the sensing protein to the T-cell claim 1 , and/or the natural killer ...

INSERTABLE VARIABLE FRAGMENTS OF ANTIBODIES AND MODIFIED ALPHA1-ALPHA2 DOMAINS OF NKG2D LIGANDS, AND NON-NATURAL NKG2D LIGANDS THAT BIND NON-NATURAL NKG2D RECEPTORS

This application relates generally to the production of polypeptides having specific antigen-binding properties of Fv domains, for example, insertable variable fragments of antibodies, and modified α1-α2 domains of NKG2D ligands. 1. A non-natural , modified α1-α2 domain of a natural NKG2D ligand molecule comprising at least 80% identity to the natural α1-α2 domain , wherein the modified α1-α2 domain has one or more amino acids of the natural α1-α2 domain replaced and wherein the modification increases its binding affinity to a non-natural NKG2D receptor ectodomain , wherein the ectodomain of the non-natural NKG2D receptor has an affinity for natural NKG2D ligands that is less than the affinity of the natural NKG2D receptor ectodomain for the natural NKG2D ligands.2. The non-natural claim 1 , modified α1-α2 domain of claim 1 , wherein the natural NKG2D ligand is any one of SEQ ID NOs: 36 claim 1 , 43 and 49-54.3. The non-natural claim 1 , modified α1-α2 domain of claim 1 , wherein the amino acids that are replaced in the natural α1-α2 domain are at three or more of positions 69 claim 1 , 71 claim 1 , 72 claim 1 , 74 claim 1 , 125 claim 1 , 152 claim 1 , 154 claim 1 , 155 claim 1 , 156 claim 1 , 157 claim 1 , 158 claim 1 , 159 and 161 of SEQ ID NO: 36 or 43.4. The non-natural claim 3 , modified α1-α2 domain of claim 3 , which comprises the amino acid sequence of SEQ ID NO.: 90 or 91.5. The non-natural claim 1 , modified α1-α2 domain of claim 1 , wherein the amino acids that are replaced from the natural α1-α2 domain are at three or more of positions 8 claim 1 , 80 claim 1 , 151 claim 1 , 154 claim 1 , 155 claim 1 , 156 claim 1 , 157 claim 1 , 158 claim 1 , and 159 of SEQ ID NO.: 16.6. The non-natural claim 1 , modified α1-α2 domain of claim 1 , wherein the amino acids that are replaced from the natural α1-α2 domain are at three or more of positions 103 claim 1 , 155 claim 1 , 156 claim 1 , 157 claim 1 , 158 claim 1 , 159 claim 1 , 162 claim 1 , and 165 of SEQ ID NO.: ...

CHIMERIC RECEPTOR WITH NKG2D SPECIFICITY FOR USE IN CELL THERAPY AGAINST CANCER AND INFECTIOUS DISEASE

The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases. 137-. (canceled)38. A Natural Killer (NK) cell expressing a chimeric receptor , the chimeric receptor comprising: 'wherein the NKG2D ligand binding domain is a functional fragment of the NKG2D of the amino acid sequence of SEQ ID NO: 12 and is capable of binding one or more native ligands of NKG2D;', 'an NKG2D extracellular ligand binding domain,'} wherein the CD3zeta cytoplasmic signaling domain recruits downstream signaling effector molecules in response to binding of a native ligand by said NKG2D extracellular receptor domain,', 'wherein the downstream signaling effector molecules trigger secretion of one or more of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFNγ); and', 'wherein the one or more native ligands are MICA, MICB, ULBP1, ULBP2, ULBP3, ULBP4, ULBP5, or ULBP6., 'a CD3zeta cytoplasmic signaling domain,'}39. The NK cell of claim 38 , wherein the CD3zeta cytoplasmic signaling domain comprises a derivative of the amino acid sequence of SEQ ID NO: 10.40. The NK cell of claim 38 , wherein the CD3zeta cytoplasmic signaling domain is at least 98% homologous to the amino acid sequence of SEQ ID NO: 10 claim 38 , wherein the NK cells exhibit a cytotoxic effect against cells of a tumor claim 38 , wherein the NK cells exhibit a cytotoxic effect of less than 20% against non-tumor cells claim 38 , and wherein the NKG2D ligand binding domain retains at least 95% of a function of a native NKG2D polypeptide.41. The NK cell of claim 38 , wherein the CD3zeta cytoplasmic signaling domain is at ...

CHIMERIC RECEPTOR WITH NKG2D SPECIFICITY FOR USE IN CELL THERAPY AGAINST CANCER AND INFECTIOUS DISEASE

The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases. 137-. (canceled)38. A method of treating a cancer using immunotherapy , the method comprising , [ 'wherein the NKG2D ligand binding domain is a functional fragment of the NKG2D of the amino acid sequence of SEQ ID NO. 12 and is capable of binding one or more native ligands of NKG2D;', 'an NKG2D extracellular ligand binding domain,'}, wherein the CD3zeta cytoplasmic signaling domain recruits downstream signaling effector molecules in response to binding of one or more of the native ligands by said extracellular receptor domain,', 'wherein the downstream signaling effector molecules trigger secretion of one or more of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFNγ),', 'wherein the one or more native ligands are MICA, MICB, ULBP1, ULBP2, ULBP3, ULBP4, ULBP5, or ULBP6; and', 'wherein the chimeric receptor enhances the cytotoxicity of the NK cell expressing the chimeric receptor as compared to a native NK cell, thereby reducing tumor burden in the subject and treating the cancer., 'a CD3zeta cytoplasmic signaling domain,'}], 'administering to a subject having the cancer a population of Natural Killer (NK) cells comprising a chimeric receptor, wherein the chimeric receptor comprises39. The method of claim 38 , wherein the CD3zeta cytoplasmic signaling domain retains at least 80% of a function of a native CD3zeta polypeptide.40. The method of claim 38 , wherein the population of NK cells has been depleted of other cell types and is therefore at least about 90% NK cells claim 38 , wherein the ...

CHIMERIC RECEPTOR WITH NKG2D SPECIFICITY FOR USE IN CELL THERAPY AGAINST CANCER AND INFECTIOUS DISEASE

The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases. 137-. (canceled)38. A method of treating a cancer using immunotherapy , the method comprising: wherein the chimeric receptor is a cell-surface receptor,', 'wherein the cell-surface receptor comprises at least two polypeptide domains not naturally found together on a single protein,', 'wherein the cell-surface receptor comprises an extracellular ligand binding domain,', 'wherein the extracellular ligand binding domain comprises an NKG2D extracellular ligand binding domain capable of binding one or more native ligands of NKG2D (NKG2DL),', 'wherein the NKG2D extracellular ligand binding domain is functional fragment of the NKG2D of the amino acid sequence of SEQ ID NO: 12,', 'wherein the cell-surface receptor further comprises a cytoplasmic signaling domain that is a derivative of the amino acid sequence of SEQ ID NO: 10,', 'wherein the cytoplasmic signaling domain retains the ability to induce secretion of one or more of GM-CSF, IFN-γ, IL-2, IL-13, or MIP-1α upon the functional fragment of the NKG2D binding an NKG2DL., 'administering to a subject having the cancer a population of engineered Natural Killer (NK) cells comprising a chimeric receptor,'}39. The method of claim 38 , wherein the proliferation of cancer cells contacted with the population of NK cells is inhibited or reduced by at least 25% as compared to cancer cells contacted with a native NK cell population.40. The method of claim 38 , wherein the cytoplasmic signaling domain is at least 98% homologous to the amino acid sequence of SEQ ID NO: 10 claim 38 , wherein the ...

CHIMERIC RECEPTOR WITH NKG2D SPECIFICITY FOR USE IN CELL THERAPY AGAINST CANCER AND INFECTIOUS DISEASE

The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases. 137-. (canceled)38. A Natural Killer (NK) cell expressing a chimeric receptor ,wherein the chimeric receptor is a cell-surface receptor,wherein the cell-surface receptor comprises at least two polypeptide domains not naturally found together on a single protein,wherein the cell-surface receptor comprises an NKG2D extracellular ligand binding domain and a CD3zeta cytoplasmic signaling domain,wherein the NKG2D ligand binding domain is a functional fragment of the NKG2D of the amino acid sequence of SEQ ID NO: 12 and is capable of binding one or more native ligands of NKG2D (NKG2DL),wherein the one or more NKG2DL are MICA, MICB, ULBP1, ULBP2, ULBP3, ULBP4, ULBP5, or ULBP6,wherein the CD3zeta cytoplasmic signaling domain is a derivative of the CD3zeta of the amino acid sequence of SEQ ID NO: 10 and retains at least 75% of the ability to activate or induce phosphorylation of one or more of CREB1, TBK1, PRK2, MEKK2, EGFR, CDK4, IRAK2, or STAT2 as compared to activation or phosphorylation resulting from a NKG2DL binding to a native NKG2D polypeptide.39. The NK cell of claim 38 , wherein the CD3zeta cytoplasmic signaling domain retains 75% to 100% of a function of a native CD3zeta polypeptide claim 38 , wherein the function of a native CD3zeta polypeptide comprises increasing cytokine secretion claim 38 , and wherein the secreted cytokine is one or more of IL-10 claim 38 , IL-12p40 claim 38 , IL-12p70 claim 38 , IL-15 claim 38 , IL-17 claim 38 , IL-1α claim 38 , IL-1β claim 38 , IL-3 claim 38 , IL-4 claim 38 , and IL-6.40. The NK cell ...

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 130-. (canceled)31. A modified macrophage or monocyte comprising a chimeric antigen receptor (CAR) ,wherein the CAR comprises an antigen binding domain, a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule, andwherein the modified macrophage or monocyte exhibits reduced SIRPα activity relative to an unmodified cell.32. The modified macrophage or monocyte of claim 31 , wherein the modified macrophage or monocyte comprises deletion of SIRPα using CRISPR/Cas9.33. The modified macrophage or monocyte of claim 31 , wherein the modified macrophage or monocyte has been treated with an anti-SIRPα antibody.34. The modified macrophage or monocyte of claim 31 , wherein the modified macrophage or monocyte comprises anti-SIRPα antibodies.35. The modified macrophage or monocyte of claim 31 , wherein the modified macrophage or monocyte comprises anti-SIRPα siRNA.36. The modified macrophage or monocyte of claim 31 , wherein the modified macrophage or monocyte exhibits increased targeted effector activity relative to an unmodified cell.37. The modified macrophage or monocyte of claim 36 , wherein the increased targeted effector activity is directed against a target cell comprising an antigen that specifically binds the antigen binding domain of the CAR.38. The modified macrophage or monocyte of claim 36 , wherein the targeted effector activity is selected from the group consisting ...

Truncated NKG2D Chimeric Receptors And Uses Thereof In Natural Killer Cell Immunotherapy

Several embodiments disclosed herein relate to the compositions comprising engineered Natural Killer (NK) cells that express a chimeric receptor, the chimeric receptor imparting to the NK cells an enhanced ability to target specific cells, such as cancerous cells or those affected by an infectious disease. Several embodiments relate to NK cells that target cells expressing natural ligands of NKG2D, where the NK cells comprise transmembrane and/or signaling domains that lead to cytotoxic and/or cytolytic effects when the NK cells bind a target cell. Uses of NK cell compositions to treat diseases are also provided for in several embodiments. 1132.-. (canceled)133. A polynucleotide encoding a chimeric receptor comprising: wherein said extracellular receptor domain comprises a peptide that binds native ligands of Natural Killer Group 2 member D (NKG2D),', 'wherein the peptide that binds native ligands of NKG2D is a fragment of NKG2D,', 'wherein the fragment of NKG2D is encoded by a polynucleotide comprising: (i) a fragment of SEQ ID NO: 1, (ii) SEQ ID NO. 2, or (iii) SEQ ID NO. 3; and, '(a) an extracellular receptor domain,'} wherein the transmembrane region comprises a CD8a hinge domain and a CD8a transmembrane domain, and', 'wherein the intracellular signaling domain comprises an OX-40 domain and CD3zeta., 'an effector domain comprising a transmembrane region and an intracellular signaling domain,'}134. The polynucleotide of claim 133 , wherein the polynucleotide further encodes claim 133 , in a bicistronic configuration claim 133 , a membrane-bound interleukin 15 (mbIL15).135. The polynucleotide of claim 134 , wherein the fragment of NKG2D is encoded by a polynucleotide comprising SEQ ID NO. 2 and wherein the mbIL15 is encoded by SEQ ID NO. 16.136. The polynucleotide of claim 134 , wherein the chimeric receptor is encoded by the nucleic acid sequence of SEQ ID NO: 90 and wherein the mbIL15 is encoded by SEQ ID NO. 16.137. The polynucleotide of claim 136 , wherein the ...

PEPTIDES FOR THE TREATMENT OF TYPE 2 DIABETES

Short peptides and peptidomimetics useful for treating Type 2 diabetes are provided, and methods for treating and/or preventing Type 2 diabetes and related conditions. 145-. (canceled)46. A peptide or peptidomimetic of 8-20 amino acids , the peptide or peptidomimetic comprising the sequence X-X-X-X-Lys-Gly-Gln-X-Thr-X-X(SEQ ID NO: 1) , wherein:{'sub': '1', 'Xis an amino acid residue other than Met and His;'}{'sub': 2', '8', '8, 'Xis absent or represents a stretch of two amino acid residues selected from the group consisting of: Arg-X, wherein Xis any amino acid residue, Asp-Met and Leu-Gln;'}{'sub': '3', 'Xis selected from the group consisting of Phe, Tyr, His, Leu, Ala, Ser and NorVal;'}{'sub': '4', 'Xis selected from Thr and Gln;'}{'sub': '5', 'Xis selected from Val and Ser;'}{'sub': '6', 'Xis a positively charged amino acid residue; and'}{'sub': '7', 'Xis absent, or represents a positively charged amino acid residue, optionally conjugated with a label.'}48. The peptide or peptidomimetic of claim 46 , comprising a sequence selected from the group consisting of X-X-X-X-Lys-Gly-Gln-Val-Thr-X-X(SEQ ID NO: 7) and Gly-X-X-X-Lys-Gly-Gln-Val-Thr-X-X(SEQ ID NO: 8) claim 46 , wherein:{'sub': '1', 'Xis an amino acid residue other than Met;'}{'sub': '2', 'Xis absent or represents Arg-Asn;'}{'sub': '3', 'Xis selected from the group consisting of Phe, Tyr, His, Leu, Ala, and NorVal;'}{'sub': '4', 'Xis Thr or Gln;'}{'sub': '6', 'Xrepresents a positively charged amino acid residue; and'}{'sub': '7', 'Xis absent or represents a positively charged amino acid residue, optionally conjugated with a label.'}50. The peptide or peptidomimetic of claim 48 , wherein X-Xrepresent Arg or Arg-Lys(Z) claim 48 , wherein Z is a detectable label connected to the epsilon amino group of the Lys residue.51. The peptide or peptidomimetic of claim 48 , comprising a sequence selected from X-Arg-Asn-X-Gln-Lys-Gly-Gln-Val-Thr-Arg-X(SEQ ID NO: 16) and Gly-Arg-Asn-X-Gln-Lys-Gly-Gln-Val-Thr-Arg-X(SEQ ID NO ...

COMPOSITIONS AND METHODS FOR IMPROVING PERSISTENCE OF CELLS FOR ADOPTIVE TRANSFER

The present application relates to the field of immunotherapy, more particularly to the manufacture of cells for adoptive cell therapy. Provided herein are compositions and methods for improving in vivo persistence of cells intended for adoptive transfer. This is achieved by making the cells less vulnerable to clearance caused by NK cells of the subject receiving the adoptive cell therapy. 1. An engineered immune cell comprising an exogenous nucleic acid molecule and at least one of:One or more endogenous genes encoding a NKG2D ligand that have been engineered to be inactivated;One or more inhibitors directed against one or more NKG2D ligands.2. The engineered immune cell of claim 1 , wherein the NKG2D ligands are selected from: MICA claim 1 , MICB claim 1 , ULBP1 claim 1 , ULBP2 claim 1 , ULBP3 claim 1 , ULBP4 claim 1 , ULBP5 and ULBP6.3. The engineered immune cell of or claim 1 , wherein the NKG2D ligand is one or both selected from MICA and MICB.4. The engineered immune cell of any one of to claim 1 , wherein the one or more inhibitors are selected from RNA inhibitors claim 1 , antibodies and peptide inhibitors.5. The engineered immune cell of any one of to claim 1 , wherein the exogenous nucleic acid molecule encodes a chimeric antigen receptor or a TCR.6. A method of rendering an immune cell less sensitive to clearance by NK cells comprising the inhibition of one or more NKG2D ligands in the immune cell.7. The method of claim 6 , wherein the immune cell further comprises an exogenous nucleic acid molecule.8. The method of claim 7 , wherein the exogenous nucleic acid molecule encodes a chimeric antigen receptor or a TCR.9. The method of any one of to claim 7 , wherein the inhibition is through genetic inactivation of one or more NKG2D ligands or by administering a NKG2D ligand inhibitor.10. The method of claim 9 , wherein the NKG2D ligand inhibitor is shRNA against one or more NKG2D ligands.11. The method according to any one of to claim 9 , wherein the ...

METHOD OF TREATING OR AMELIORATING METABOLIC DISORDERS USING CLEC-2

Methods of treating metabolic diseases and disorders using a Clec-2 extracellular domain are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, elevated glucose levels, elevated insulin levels and elevated triglyceride levels. 1. A method of treating a metabolic condition in a subject , comprising administering to the subject in need thereof a therapeutically effective amount of a Clec-2 inhibitor , wherein the Clec-2 inhibitor comprises the extracellular domain of the Clec-2 receptor or a fragment thereof.2. The method of claim 1 , wherein in the metabolic condition is diabetes claim 1 , an elevated glucose level claim 1 , an elevated insulin level claim 1 , an elevated triglyceride level claim 1 , insulin resistance or poor oral glucose tolerance.3. The method of claim 2 , wherein the diabetes is type II diabetes.4. The method of wherein the extracellular domain of the Clec-2 receptor or fragment thereof is the conjugated to an immuglobulin constant region or fragment thereof.5. The method of claim 4 , wherein the extracellular domain of the Clec-2 receptor or fragment thereof is a human extracellular domain or fragment thereof.6. The method of wherein the immunoglobulin constant region is a human immunoglobulin constant region or fragment thereof.7. The method of claim 6 , wherein the Clec-2 inhibitor comprises a polypeptide encoded by a polynucleotide which comprises a sequence having at least 90% sequence identity with that of SEQ ID 2 claim 6 , 4 claim 6 , 6 or 13.8. The method of claim 7 , wherein the Clec-2 inhibitor comprises a polypeptide encoded by a polynucleotide which comprises a sequence having at least 95% sequence identity with that of SEQ ID 2 claim 7 , 4 claim 7 , 6 or 13.9. The method of claim 8 , wherein the Clec-2 inhibitor comprises a polypeptide encoded by a polynucleotide which comprises a sequence having at least 98% sequence identity with that of SEQ ID 2 claim 8 , 4 claim 8 , 6 or 13.10. The method of ...

METHODS AND COMPOSITIONS FOR CELLULAR IMMUNOTHERAPY

The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions. 1. A modified T cell , comprising a chromosomal MNK gene knock out , wherein the MNK gene comprises the MNK1 gene , the MNK2 gene , or both; optionally further comprising a transgene encoding an engineered antigen specific receptor.26-. (canceled)7. The modified T cell of claim 1 , wherein the encoded engineered antigen specific receptor is a chimeric antigen receptor (CAR) claim 1 , a T cell receptor (TCR) claim 1 , a TCR-CAR claim 1 , or any combination thereof.8. The modified T cell of claim 7 , wherein the encoded CAR comprises a binding domain comprising an scFv that specifically binds to the antigen.9. The modified T cell of claim 7 , wherein the encoded CAR comprises at least one signaling domain.10. The modified T cell of claim 7 , wherein the encoded T cell receptor is an enhanced affinity TCR.11. The modified T cell of claim 7 , wherein the encoded TCR is an αβ TCR or a γδ TCR.12. The modified T cell of claim 1 , wherein both MNK1 and MNK2 are knocked out.13. The modified T cell of claim 1 , wherein the antigen is a tumor antigen claim 1 , a pathogenic microorganism antigen claim 1 , or an autoimmune disease antigen.14. The modified T cell of claim 13 , wherein the tumor antigen is selected from the group consisting of human immunodeficiency virus (HIV) antigens claim 13 , hepatitis C virus (HCV) antigens claim 13 , hepatitis B virus (HBV) antigens claim 13 , cytomegalovirus (CMV) antigens claim 13 , Epstein Barr virus (EBV) antigens claim 13 , parasitic antigens claim 13 , and tumor antigens claim 13 , such as ROR1 claim 13 , EGFR claim 13 , EGFRvIII claim 13 , HPV E6 claim 13 , HPV E7 claim 13 , L1-CAM claim 13 ...

PHOSPHOLIPASE A2 RECEPTOR ANTIGENS AND THEIR MEDICAL USE

The present invention relates to a non-naturally occurring peptide comprising amino acid sequence S-V-L-T-X1-E-N-X2 (SEQ ID NO: 1), wherein X1 is any amino acid and X2 is any amino acid, which may optionally be linked to an amino acid sequence X3-I-X4-X5-E-X6 (SEQ ID NO: 5), wherein, X3, X4, X5 and X6 each denote any amino acid. The present invention further relates to the use of such peptides as a medicament such as for the prevention and treatment of kidney disease and in apheresis methods. 1. A non-naturally occurring peptide comprising amino acid sequence S-V-L-T-X1-E-N-X2 (SEQ ID NO: 1) , wherein X1 is any amino acid and X2 is any amino acid.2. The peptide according to claim 1 , wherein the peptide is a variant peptide comprising the amino acid sequence SVLTEENC (SEQ ID NO: 2) or SVLTEENS (SEQ ID NO: 3).3. The peptide of claim 1 , wherein the peptide comprises:A C-terminal domain comprising the amino acid sequence S-V-L-T-X1-E-N-X2 (SEQ ID NO: 1)An N-terminal domain comprising the amino acid sequence X3-I-X4-X5-E-X6 (SEQ ID NO: 5), wherein, X3, X4, X5 and X6 each denote any amino acid.4. The peptide according to claim 3 , wherein X3 is V or P; X4 is Q claim 3 , D or E; X5 is S claim 3 , D or E and X6 is S claim 3 , D or E.5. The peptide according to claim 1 , wherein the peptide is a variant peptide comprising the amino acid sequence S-V-L-T-X1-E-N-X2-K (SEQ ID NO: 6).6. The peptide of claim 3 , wherein the N-terminal domain comprises the variant peptide comprising the amino acid sequence X3-I-X4-X5-E-X6-L-K (SEQ ID NO: 8).7. The peptide according to claim 3 , wherein the peptide comprises a linker between the N-terminal and C-terminal domains.8. The peptide according to claim 7 , wherein the linker is selected from a group consisting of: a peptide linker claim 7 , a synthetic linker claim 7 , a combination of peptide and synthetic linker.9. (canceled)10. The peptide according to claim 8 , wherein the peptide linker comprises 5 glycine residues claim 8 , the ...

Non-Human Animals Comprising a Humanized ASGR1 Locus

Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms. 1. A non-human animal or non-human animal genome comprising a genetically modified endogenous Asgr1 locus encoding a modified Asgr1 protein , wherein the modified Asgr1 protein comprises a cytoplasmic domain , a transmembrane domain , and an extracellular domain , and all or part of the extracellular domain is encoded by a segment of the endogenous Asgr1 locus that has been deleted and replaced with an orthologous human ASGR1 sequence , andwherein the non-human animal expresses the modified Asgr1 protein.2. The non-human animal or non-human animal genome of claim 1 , wherein the extracellular domain comprises a coiled-coil domain and a C-type lectin domain claim 1 , and all or part of the C-type lectin domain is encoded by the segment of the endogenous Asgr1 locus that has been deleted and replaced with an orthologous human ASGR1 sequence.3. The non-human animal or non-human animal genome of claim 2 , wherein the C-type lectin domain is a human ASGR1 C-type lectin domain.4. The non-human animal or non-human animal genome of claim 2 , wherein the C-type lectin domain comprises the sequence set forth in SEQ ID NO: 28.5. The non-human animal or non-human animal genome of claim 1 , wherein the extracellular domain comprises a coiled-coil domain and a C-type lectin domain claim 1 , and all or part of the coiled- ...

PEPTIDE COMPOSITIONS THAT DOWNREGULATE TLR-4 SIGNALING PATHWAY AND METHODS OF PRODUCING AND USING SAME

Peptide compositions are disclosed that include fragments of surfactant protein-A, or a derivative thereof, wherein the fragment binds to TLR4. Methods of producing and using the peptide compositions are also disclosed.

Novel alternative splice transcripts for mhc class i related chain alpha (mica) and uses thereof

The present invention relates to novel alternative splice transcripts (AST) for MICA (MHC class I related chain alpha) encoding novel MICA protein isoforms and uses thereof. In particular, the present invention relates to an isolated polypeptide at least 80% of identity with a sequence selected from the group consisting of SEQ ID NO:1 (MICA-A), SEQ ID NO:2 (MICA-B1), SEQ ID NO:3 (MICA-B2); SEQ ID NO:4 (MICA-C) and SEQ ID NO: (MICA-D).

TREATMENT OF lge-MEDIATED DISEASE

The methods and compositions described herein are based, in part, on the discovery of a polypeptide of soluble CD23 (sCD23) that binds and sequesters IgE. Thus, the sCD23 peptides, polypeptides and derivatives described herein are useful for treating conditions or disorders involving increased IgE levels such as e.g., allergy, anaphylaxis, inflammation, lymphoma, and certain cancers. 1. (canceled)2. A compound of the formula X—R(SEQ ID NO: 214) , wherein Rcomprises SEQ ID NO: 4 and XcomprisesTT QSLKQLEERA ARNVSQVSKN LESHHGDQMA QKSQSTQISQ ELEELRAEQQ RLKSQDLELS WNLNGLQADL SSFKSQELNE RNEASDLLER LREEVTKLRM ELQVS (SEQ ID NO: 7), or a contiguous fragment of at least 15 amino acids of SEQ ID NO: 7.3. The compound of claim 2 , wherein the compound is PEGylated.4. The compound of claim 2 , wherein the compound comprises a high affinity binding site for IgE.5. The compound of claim 4 , wherein the high affinity binding site is formed by the amino acid substitution D107E of SEQ ID NO: 4.6. The compound of claim 2 , further comprising a pharmaceutically acceptable carrier.7. A method for reducing a subject's immune response to an allergen claim 2 , the method comprising: administering to a subject a pharmaceutical composition containing an effective amount of a compound selected from:{'sub': 1', '0', '0', '1, 'a compound of formula X—R(SEQ ID NO: 214), wherein Rcomprises SEQ ID NO: 4 and Xcomprises TT QSLKQLEERA ARNVSQVSKN LESHHGDQMA QKSQSTQISQ ELEELRAEQQ RLKSQDLELS WNLNGLQADL SSFKSQELNE RNEASDLLER LREEVTKLRM ELQVS (SEQ ID NO: 7), or a contiguous fragment of at least 15 amino acids of SEQ ID NO: 7,'}{'sub': 0', '2', '0', '2, 'a compound of formula R—X(SEQ ID NO: 215), wherein Rcomprises SEQ ID NO: 4 and Xcomprises SEGSAE (SEQ ID NO: 9), SEGSA (SEQ ID NO: 10), SEGS (SEQ ID NO: 11), SEG, SE, S, L, or —COOH, and'}{'sub': 1', '0', '2', '0', '1', '2, 'a compound of formula X—R—X(SEQ ID NO: 216), wherein Rcomprises SEQ ID NO: 4, Xcomprises at least 15 contiguous amino acids of TT ...

BREAST AND OVARIAN CANCER VACCINES

The compositions described herein include an epitope of a peptide that may elicit an immune response in a subject following administration. The compositions may comprise nucleic acids. The compositions may comprise peptides. The methods described herein include administering a composition comprising an epitope of a peptide to a subject in need thereof. 1. A composition comprising:a) an isolated and purified plasmid comprising a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises a plurality of epitopes; andb) an excipient.2. The composition of claim 1 , wherein the plurality of epitopes comprises one or more epitopes comprising at least 90% sequence identity to an amino acid sequence selected from SEQ ID NOs: 1 claim 1 , 6 claim 1 , 8-10 claim 1 , 14-16 claim 1 , 20 claim 1 , 25-28 claim 1 , 32-34 claim 1 , 46-56 claim 1 , 60-62 claim 1 , 66-75 claim 1 , 82-85 claim 1 , or 87.3. The composition of or claim 1 , wherein the plurality of epitopes comprises one or more epitopes comprising at least 90% sequence identity to an amino acid sequence selected from SEQ ID NOs: 82-84.4. The composition of or claim 1 , wherein the plurality of epitopes comprises one or more epitopes comprising at least 90% sequence identity to an amino acid sequence selected from SEQ ID NOs: 1 claim 1 , 6 claim 1 , 8-10 claim 1 , 14-16 claim 1 , 20 claim 1 , 25-28 claim 1 , or 32-34.5. The composition of or claim 1 , wherein the plurality of epitopes comprises one or more epitopes comprising at least 90% sequence identity to an amino acid sequence selected from SEQ ID NOs: 46-56 claim 1 , 60-62 claim 1 , or 66-75.6. The composition of or claim 1 , wherein the plurality of epitopes comprises one or more epitopes comprising at least 90% sequence identity to an amino acid sequence selected from SEQ ID NOs: 54 claim 1 , 73 claim 1 , 85 claim 1 , or 87.7. The composition of claim 1 , wherein the plurality of epitopes comprises one or more epitopes selected from SEQ ID NOs: 1 ...

Compositions and methods for nucleic acid and/or protein payload delivery

Provided are methods and compositions for nanoparticle delivery of payloads (e.g., nucleic acid and/or protein payloads) to cells. In some embodiments, a subject nanoparticle includes a core and a sheddable layer encapsulating the core, where the core includes (i) an anionic polymer composition; (ii) a cationic polymer composition; (iii) a cationic polypeptide composition; and (iv) a nucleic acid and/or protein payload; and where: (a) the anionic polymer composition includes polymers of D-isomers of an anionic amino acid and polymers of L-isomers of an anionic amino acid, and/or (b) the cationic polymer composition comprises polymers of D-isomers of a cationic amino acid and polymers of L-isomers of a cationic amino acid. In some cases, the polymers of D-isomers of an anionic and/or cationic amino acid are present at a ratio, relative to the polymers of L-isomers, in a range of from 10:1 to 1:10.

Compositions comprising e-selectin antagonists and uses therefor

This invention discloses the use of an E-selectin antagonist and a mobilizer of hematopoietic stem cells or progenitor cells in methods and compositions for treating or preventing immunocompromised conditions resulting from medical treatment. The present invention is particular relevant for prophylaxis and/or treatment of hematopoeitic disorders including neutropenia, agranulocytosis, anemia and thrombocytopenia in individuals receiving or proposed to receive treatments that target rapidly dividing cells or that disrupt the cell cycle or cell division.

Inhibitors

The invention provides a portion of multimerin 2 (MMRN2) or a variant thereof, that inhibits the interaction between CLEC14A and MMRN2, in addition to a portion of MMRN2 or a variant thereof, that inhibits the interaction between CD93 and MMRN2. The invention provides compounds comprising said portions and either a cytotoxic moiety or a detectable moiety.

TREATMENT AND DIAGNOSIS OF CANCER OR INFECTIOUS DISEASE USING RECOGNITION MECHANISM OF T CELL RECEPTOR

To provide a therapy and a diagnosis of cancer or an infection using recognition mechanism of a T-cell receptor. An NK cell function enhancer comprises, an active ingredient, a T-cell receptor chimeric protein being a fusion protein of: a T-cell receptor variable region capable of recognizing a cancer-specific antigen or a T-cell receptor variable region capable of recognizing an antigen specific to a pathogen causative of an infection, and an immunoglobulin Fc region, wherein the T-cell receptor chimeric protein binds to an MHC molecular complex of a cancer cell to down-modulate an MHC class I molecule complex, and the cancer cell is killed or damaged by recognition of an NK cell; and an NK cell function enhancer for imparting to an NK cell a function of recognizing a cancer cell or an infected cell infected with a pathogen causative of an infection, which expresses an MHC class I molecule, and killing or damaging the cancer cell or the infected cell by TDCC (T-cell receptor chimeric protein-dependent cellular cytotoxicity) activity. 1. An NK cell function enhancer comprising , as an active ingredient , a T-cell receptor chimeric protein being a fusion protein of a T-cell receptor variable region capable of recognizing a cancer-specific antigen and an immunoglobulin Fc region ,wherein the T-cell receptor chimeric protein binds to an MHC molecular complex of a cancer cell to reduce the expression of an MHC class I molecular complex and the cancer cell is killed or damaged by recognition of an NK cell orwherein the enhancer is for imparting a recognition function of a cancer cell expressing an MHC class I molecule to an NK cell to kill or damage the cancer cell by TDCC (T-cell receptor chimeric protein-dependent cellular cytotoxicity) activity.2. (canceled)3. The NK cell function enhancer according to claim 1 , wherein the T-cell receptor chimeric protein comprises all of the T-cell receptor variable region and CDR3 claim 1 , and a J region.4. The NK cell function ...

GENETICALLY ENGINEERED HEMATOPOIETIC STEM CELLS AND USES THEREOF

Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins. 1. An isolated population of cells comprising a plurality of hematopoietic cells (HCs) , wherein the plurality of HCs comprises(i) a genetically engineered gene encoding CD33 that is engineered to have reduced or eliminated expression of CD33, and(ii) a genetically engineered gene encoding CLL1 that is engineered to have reduced or eliminated expression of CLL1.2. The isolated population of cells of claim 1 , wherein the genetically engineered gene encoding CLL1 or CD33 comprises a frameshift mutation.3. The isolated population of cells of claim 1 , wherein the genetically engineered gene encoding CLL1 or CD33 is modified such that an exon is skipped.4. The isolated population of cells of claim 1 , wherein the genetically engineered gene encoding CLL1 or CD33 comprises an indel mutation.5. The isolated population of cells of claim 1 , wherein the genetically engineered HCs are genetically engineered using a zinc finger nuclease (ZFN) or a transcription activator-like effector-based nuclease (TALEN).6. The isolated population of cells of claim 1 , wherein the genetically engineered HCs are genetically engineered using a CRISPR system comprising a guide nucleic acid.7. The isolated population of cells of claim 6 , wherein the guide nucleic acid comprises a sequence according to SEQ ID NO: 67 or a complement thereof.8. The isolated population of cells of claim 6 , wherein the guide nucleic acid comprises a sequence according to SEQ ID NO: 137 or a complement thereof.9. The isolated population of cells of claim 1 , wherein exon 3 of the genetically engineered gene encoding CD33 is genetically engineered.10. The isolated population of cells of claim 1 , wherein exon 4 of the ...

METHODS AND AGENTS FOR TREATING ALZHEIMER'S DISEASE

The present disclosure provides compositions and methods useful for treating or preventing diseases or disorders where beta amyloid accumulation or aggregation contributes to the pathology or symptomology of the disease, for example Alzheimer's disease. 1. A method of treating a neuro-inflammation disorder in a subject , the method comprising administering to a subject in need thereof an effective amount of an agent that inhibits or reduces the expression or activity of CD33 protein , wherein the agent is selected from the group consisting of antibodies and antigen binding fragments thereof , small or large organic or inorganic molecules , peptidomimetics , monosaccharides , disaccharides , trisaccharides , oligosaccharides , polysaccharides , lipids , and glycosaminoglycans.2. The method of claim 1 , wherein the agent is an antibody or a small molecule a small molecule selected from the group consisting of sialic acid analogues and derivatives.3. The method of claim 1 , wherein the agent is a monoclonal antibody.4. The method of claim 1 , wherein the agent is a humanized antibody.5. The method of claim 1 , wherein the agent is an anti-CD33 antibody or an antigen binding fragment thereof.6. The method of claim 1 , wherein the agent is a small molecule selected from the group consisting of sialic acid analogues and derivatives.7. The method of claim 1 , wherein the agent crosses or is formulated to cross the blood-brain barrier.8. The method of claim 1 , wherein the neuro-inflammation disorder is a neurodegenerative disease or disorder.9. The method of claim 8 , wherein the neurodegenerative disease or disorder is selected from the group consisting of Alzheimer's disease (AD) claim 8 , Lewy body dementia claim 8 , Parkinson's disease (PD) claim 8 , Huntington's Disease claim 8 , Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS).10. The method of claim 9 , wherein the neurodegenerative disease or disorder is Alzheimer's disease or Lewy body dementia.11. ...

ADOPTIVE T-CELL THERAPY USING FceRI-BASED CHIMERIC ANTIGEN RECEPTORS FOR TREATING IgE-MEDIATED ALLERGIC DISEASES

A chimeric antigen receptor (CAR) contains a human FcεRIα extracellular domain or a mutant FcεRIα extracellular domain that has a reduced binding affinity for human IgE compared to wild type human FcεRIα extracellular domain. The CAR further contains an intracellular signaling domain comprising at least one immunoreceptor-based activation motif (ITAM). The CAR may further comprise a costimulatory signaling domain, such as an intracellular domain of at least one of the costimulatory molecules 4-1BB, CD27, CD28, CD134 or ICOS. T cells transduced with vectors encoding the CAR are used in CAR-based adoptive T-cell therapy for targeting IgE-expressing B cells and treating IgE-mediated allergic diseases.

A CELL COMPRISING A CHIMERIC ANTIGEN RECEPTOR (CAR)

The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) which comprises an antigen binding domain and an intracellular signalling domain; (ii) a membrane tethering component (MTC) which comprises a first dimerization domain; and (Hi) a signal-dampening component (SDC) comprising a signal-dampening domain (SDD) and a second dimerization domain which specifically binds the first dimerisation domain of the membrane-tethering component. Dimerisation between the MTC and SDC may be controllable with an agent, meaning that the agent can be used to control CAR-mediated cell signalling. 1. A cell which comprises:(i) a chimeric antigen receptor (CAR) which comprises an antigen binding domain and an intracellular signalling domain;(ii) a membrane tethering component which comprises a first dimerization domain; and(iii) a signal-dampening component (SDC) comprising a signal-dampening domain (SDD) and a second dimerization domain which specifically binds the first dimerisation domain of the membrane-tethering component.2. A cell according to claim 1 , wherein the SDD inhibits the intracellular signalling domain of the CAR.3. A cell according to claim 2 , wherein the SDD comprises a phosphatase domain capable of dephosphorylating immunoreceptor tyrosine-based activation motifs (ITAMs).49.-. (canceled)10. A cell according to claim 1 , wherein the SDD causes the removal of the intracellular signalling domain of the CAR.11. A cell according to claim 10 , wherein the SDD comprises a protease and the CAR comprises a protease cleavage site.12. (canceled)13. A cell according to wherein binding of the first and second dimerization domains is controllable by the presence or absence of an agent.14. A cell according to claim 13 , wherein binding of the first and second dimerization domains is induced by the presence of a chemical inducer of dimerisation (CID).1518.-. (canceled)19. A cell according to claim 13 , wherein the agent disrupts binding of the ...