НУКЛЕИНОВАЯ КИСЛОТА, СОДЕРЖАЩАЯ ИЛИ КОДИРУЮЩАЯ ГИСТОНОВУЮ СТРУКТУРУ ТИПА"СТЕБЕЛЬ-ПЕТЛЯ" И ПОЛИ(А)-ПОСЛЕДОВАТЕЛЬНОСТЬ ИЛИ СИГНАЛ ПОЛИАДЕНИЛИРОВАНИЯ, ДЛЯ УВЕЛИЧЕНИЯ ЭКСПРЕССИИ КОДИРУЕМОГО ОПУХОЛЕВОГО АНТИГЕНА

Настоящее изобретение относится к области биотехнологии, конкретно к молекуле мРНК, содержащей кодирующую область, кодирующую содержащий опухолевый антиген белок, по меньшей мере, одну гистоновую структуру типа «стебель-петля» и поли(A)-последовательность или сигнал полиаденилирования, и может быть использовано в медицине. Изобретение позволяет получить нуклеиновую кислоту для увеличения экспрессии указанного кодируемого пептида или белка. Объединение в структуре нуклеиновой кислоты сигнала полиаденилирования и гистоновой структуры типа «стебель-петля» за счет синергетического эффекта позволяет в несколько раз повысить уровень экспрессии по сравнению с таким уровнем каждого из таких элементов, используемых в отдельности. 8 н. и 17 з.п. ф-лы, 27 ил., 15 табл., 3 пр.

КОМПОЗИЦИИ И СПОСОБЫ ИММУНОТЕРАПИИ

Настоящее изобретение относится к иммунологии. Предложена Т-клетка для снижения опухолевой нагрузки и/или лечения неоплазии, содержащая T-клеточный рецептор (TCR) или химерный рецептор антигена (CAR), который связывается с антигеном В-клеточного лейкоза, и ингибирующий химерный рецептор антигена (iCAR), который содержит домен внутриклеточной передачи сигнала CTLA-4 или PD-1. Кроме того, описано применение такой Т-клетки для снижения опухолевой нагрузки и/или размера опухоли и фармацевтическая композиция. Также представлены вектор, композиция и способ получения Т-клетки. Использование iCAR позволяет снизить цитотоксичность Т-клетки в отношении клеток ненеопластической ткани. 8 н. и 10 з.п. ф-лы, 23 ил., 1 пр.

КОМПОЗИЦИИ И СПОСОБЫ ДЛЯ ИММУНОТЕРАПИИ

Настоящее изобретение относится к иммунологии. Предложена Т-клетка, содержащая химерный рецептор антигена (CAR) и химерный костимулирующий рецептор (CCR), а также способ получения такой клетки. Описаны способы индукции гибели клеток опухоли, лечения и предотвращения неоплазмы, фармацевтическая композиция и набор для иммунотерапии. Связывание CCR с антигеном обеспечивает доставку костимулирующего сигнала к Т-клетке, что обеспечивает более высокую степень цитолитической активности. 7 н. и 44 з.п. ф-лы, 6 ил., 1 табл., 1 пр.

БИОМАРКЕР ДЛЯ МОНИТОРИНГА ПАЦИЕНТОВ

Группа изобретений относится к медицине, а именно к иммунологии, и может быть использована для определения еx-vivo эффективности лечения рака. Для этого после введения одной или более доз иммуногенной композиции субъекту измеряют уровень активированных Т-лимфоцитов (CD3+ CD69+) в организме. Уровень активированных Т-лимфоцитов (CD3+ CD69+) выше приблизительно 10,4% свидетельствуют о том, что субъект является таким, который демонстрирует успешный клинический выход для лечения, то есть повышение коэффициента выживания. Использование уровня активированных Т-лимфоцитов (CD3+ CD69+) позволяет применять их в качестве биомаркера для мониторинга, модификации или корректировки лечения рака. 2 н. и 5 з.п. ф-лы, 1 пр., 2 ил.

КОМБИНИРОВАННОЕ ЛЕКАРСТВЕННОЕ СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ РАКА С ИСПОЛЬЗОВАНИЕМ ПОКСВИРУСА, ЭКСПРЕССИРУЮЩЕГО ОПУХОЛЕВЫЙ АНТИГЕН, И АНТАГОНИСТА И/ИЛИ АГОНИСТА ИНГИБИТОРА ИМУННОЙ КОНТРОЛЬНОЙ ТОЧКИ

Предложенная группа изобретений относится к области медицины. Предложено терапевтическое средство для лечения человека, имеющего рак, содержащее рекомбинантный ортопоксвирус MVA-BN и антагонист анти-PD-1, который представляет собой антитело. Предложен способ лечения человека, имеющего рак, включающий введение пациенту рекомбинантного ортопоксвируса MVA-BN и вышеуказанного антагониста. Предложенная группа изобретений обеспечивает достижение синергетического эффекта, который связан с рекомбинантным ортопоксвирусом и антагонистом анти-PD-1. 2 н. и 20 з.п. ф-лы, 23 ил., 24 пр.

КОМПОЗИЦИЯ, ВКЛЮЧАЮЩАЯ КОМПЛЕКСНУЮ (И)РНК И СВОБОДНУЮ ИРНК ДЛЯ ОСУЩЕСТВЛЕНИЯ ИЛИ ПОВЫШЕНИЯ ИММУНОСТИМУЛИРУЮЩЕГО ОТВЕТА У МЛЕКОПИТАЮЩИХ, И ЕЕ ПРИМЕНЕНИЯ

Группа изобретений относится к иммуностимулирующей композиции, включающей а) адъювантный компонент, содержащий или состоящий по меньшей мере из одной (и)РНК, объединенной с поликатионным пептидом или белком, и б) по меньшей мере одну свободную иРНК, кодирующую по меньшей мере один антиген, причем иммуностимулирующая композиция способна индуцировать или усиливать врожденный и необязательно адаптивный иммунный ответ у млекопитающего. Мольное соотношение (и)РНК адъювантного компонента а) к по меньшей мере к одной свободной иРНК второго компонента б) иммуностимулирующей композиции находится в пределах от примерно 0,001:1 до примерно 1:0,001. Иммуностимулирующая композиция по настоящему изобретению может являться как фармацевтической композицией, так и вакциной. Группа изобретений также относится к способу получения иммуностимулирующей композиции и ее применению для лечения различных заболеваний. Группа изобретений эффективна в индукции и усилении иммунного ответа у млекопитающего, а также в ...

КОМПОЗИЦИЯ И ВАКЦИНА ДЛЯ ЛЕЧЕНИЯ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ

КОНЪЮГАТ ПОЛИПЕПТИД-НУКЛЕИНОВАЯ КИСЛОТА ДЛЯ ИММУНОПРОФИЛАКТИКИ ИЛИ ИММУНОТЕРАПИИ НЕОПЛАСТИЧЕСКИХ ИЛИ ИНФЕКЦИОННЫХ ЗАБОЛЕВАНИЙ

... 1. Выделенный конъюгат антитело-нуклеиновая кислота или пептид-нуклеиновая кислота, содержащий: ! i) антитело или пептид, которые специфически связываются с клеточным компонентом ! а) опухолевой клетки; ! b) сосудистой сети опухоли и/или ! c) компонента микроокружения опухоли, и ! ii) одну или несколько иммуностимуляторных последовательностей нуклеиновых кислот (INAS), где одна или несколько из этих последовательностей нуклеиновых кислот содержат ассоциированную с патогеном молекулярную структуру (PAMP). ! 2. Конъюгат по п.1, где антитело выбрано из группы, состоящей из мультиспецифического антитела, антитела человека, гуманизированного антитела, химерного антитела, одноцепочечного антитела, Fab-фрагмента, F(ab')-фрагмента и антиидиотипического (анти-Id) антитела. ! 3. Конъюгат по п.1, где клеточным компонентом является опухолеспецифический антиген или молекула клеточной поверхности. ! 4. Конъюгат по п.1, где клеточный компонент выбран из группы, состоящей из рецепторов факторов роста, ...

НОВЫЕ ПЕПТИДЫ И КОМБИНАЦИИ ПЕПТИДОВ ДЛЯ ПРИМЕНЕНИЯ В ИММУНОТЕРАПИИ РАКА ЛЕГКИХ, В ТОМ ЧИСЛЕ НЕМЕЛКОКЛЕТОЧНОГО РАКА ЛЕГКИХ (НМРЛ) И ДРУГИХ ВИДОВ РАКА

НУКЛЕИНОВАЯ КИСЛОТА, СОДЕРЖАЩАЯ ИЛИ КОДИРУЮЩАЯ ГИСТОНОВУЮ СТРУКТУРУ ТИПА "СТЕБЕЛЬ-ПЕТЛЯ" И ПОЛИ(A)-ПОСЛЕДОВАТЕЛЬНОСТЬ ИЛИ СИГНАЛ ПОЛИАДЕНИЛИРОВАНИЯ, ДЛЯ УВЕЛИЧЕНИЯ ЭКСПРЕССИИ КОДИРУЕМОГО ОПУХОЛЕВОГО АНТИГЕНА

КОМПОЗИЦИЯ, ВКЛЮЧАЮЩАЯ КОМПЛЕКСНУЮ (и)РНК И СВОБОДНУЮ иРНК ДЛЯ ОСУЩЕСТВЛЕНИЯ ИЛИ ПОВЫШЕНИЯ ИММУНОСТИМУЛИРУЮЩЕГО ОТВЕТА У МЛЕКОПИТАЮЩИХ, И ЕЕ ПРИМЕНЕНИЯ

... 1. Иммуностимулирующая композиция, включающая ! а) адъювантный компонент, включающий или состоящий по меньшей мере из одной (и)РНК, объединенный с катионным или поликатионным соединением, и ! б) по меньшей мере одну свободную иРНК, кодирующую по меньшей мере один терапевтически активный белок, антиген и/или антитело, ! причем иммуностимулирующая композиция способна индуцировать или усиливать врожденный и необязательно адаптивный иммунный ответ у млекопитающего. ! 2. Иммуностимулирующая композиция по п.1, в которой по меньшей мере одна (и)РНК адъювантного компонента, выбрана из короткого олигонуклеотида РНК, кодирующей РНК, включая иРНК, иммуностимулирующей РНК, миРНК, антисмысловой РНК или РНК-переключателей, рибозимов или аптамеров. ! 3. Иммуностимулирующая композиция по п.1 или 2, в которой по меньшей мере одной (и)РНК адъювантного компонента является иРНК. ! 4. Иммуностимулирующая композиция по одному из п.1 или 2, в которой по меньшей мере одна свободная иРНК и по меньшей мере одна ...

ИММУНОГЕННЫЕ КОМПОЗИЦИИ, СОДЕРЖАЩИЕ CEA, MUC1 И TERT

КОМПОЗИЦИЯ ВАКЦИНЫ ДЛЯ ТРАНСДЕРМАЛЬНОГО ИЛИ ТРАНСМУКОЗАЛЬНОГО ВВЕДЕНИЯ

... 1. Композиция вакцины для трансдермального или трансмукозального введения для применения при индукции клеточного иммунитета, причем вакцина содержит:(i) антиген и(ii) фармакологически приемлемую кислоту или ее фармакологически приемлемую соль в качестве первого стимулятора индукции клеточного иммунитета.2. Композиция вакцины по п.1, отличающаяся тем, что композиция предназначена для применения при лечении рака.3. Композиция вакцины по п.1, отличающаяся тем, что композиция предназначена для применения при лечении вирусного заболевания.4. Композиция вакцины по любому из пп.1-3, отличающаяся тем, что фармакологически приемлемая кислота или ее фармакологически приемлемая соль представляет собой органическую кислоту или ее фармакологически приемлемую соль.5. Композиция вакцины по п.4, отличающаяся тем, что органическая кислота или ее фармакологически приемлемая соль представляет собой органическое соединение, имеющее карбоксильную группу, или органическое соединение, имеющее сульфогруппу, или ...

DNS IMPFUNG

Tumorvakzine für MUC1-positive Karzinome

The invention relates to vaccines which are based on the molecular structure of human epithelial mucin, MUC1, for combating tumour cells which have remained in the body after surgery or another type of primary therapy (minimal residual disease). Said vaccines are characterised in that they carry O-glycosidically bonded a-N-acetylgalactosamine (GalNAc) or short-chained oligosaccharides on the threonine of the immunodominant region (amino acid sequence PDTRPAP). The inventive vaccines can be used in principle for all MUC1-positive carcinomas.

COMPOSITION AND VACCINE FOR TREATING LUNG CANCER

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

VERWENDUNG EINER MEHRKOMPONENTEN-TUMORVAKZINE

PRODUCTION OF LARGE ONES LIPOSOME BY INFUSION IN PEG

SUGGESTION OF ANSWERS of CYTOTOXIC t LYMPHOZYTEN

MUCIN MANNAN KONJUGATE ONE AND YOUR IMMUNOTHERAPEUTI APPLICATION

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

CHIMÄRES PLANT VIRUS WITH PEPTIDEN OF MUCIN

Yeast-MUC1 immunotherapeutic compositions and uses thereof

Disclosed are yeast-based immunotherapeutic compositions comprising mucin-I (MUC1), as well as methods for the prevention and/or treatment of cancers characterized by the expression or overexpression of mucin-1 (MUC1).

Methods and compositions for Dectin-2 stimulation and cancer immunotherapy

Provided are methods and compositions for treating an individual with cancer or infectious disease. Multivalent Dectin-2 stimulating agents are provided that include: (a) an agent that binds to Dectin-2 and stimulates Dectin-2 signaling; and (b) an antibody and/or an immunomodulatory agent, wherein (a) and (b) are conjugated to one another. In some cases, (a) is a mannobiose glycopolypeptide that binds to Dectin-2. In some cases (b) is a stimulatory ligand for a TLR (e.g., TLR7, TLR8, TLR7/8, TLR2, and the like). Methods of treating an individual with cancer and/or an infectious disease can include administering to the individual an effective amount of a Dectin-2 stimulating composition. In some cases, the Dectin-2 stimulating composition comprises a Dectin-2 stimulating glycopolymer. In some cases the Dectin-2 stimulating composition comprises a multivalent Dectin-2 stimulating agent.

Precision glycoconjugates as therapeutic tools

The present description relates to glycoconjugates, glycoconjugate immunogens and glycoconjugate vaccines comprising carbohydrate antigens coupled to immunogenic carrier proteins, or materials used for detection and screening of resulting antibodies. Improved methods of more directly and precisely conjugating carbohydrate antigens to free thiol groups of immunogenic carrier proteins are described, including "click-chemistry" approaches based on photocatalytic thiol-ene reactions.

Modulation of cytokine signaling regulators and applications for immunotherapy

Scaffolds for cell transplantation

A device that includes a scaffold composition and a bioactive composition with the bioactive composition being incorporated into or coated onto the scaffold composition such that the scaffold composition and/or a bioactive composition controls egress of a resident cell or progeny thereof. The devices mediate active recruitment, modification, and release of host cells from the material.

Vaccine nanotechnology

Methods and compositions for improving immune responses

Scaffolds for cell transplantation

Preparation of inactivated artificial antigen presenting cells and their use in cell therapies

Methods of processing inactivated artificial antigen presenting cells (aAPCs) and artificial antigen presenting cells with specificity for selected antigenic peptides are described, including their generation and use in cell therapy compositions comprising activated cytotoxic T lymphocytes. Inactivated aAPCs are advantageously generated through crosslinking, such as via a photoreaction involving a psoralen derivative and UVA irradiation.

MUC-1 antigen with reduced number of VNTR repeat units

Antibody to Mucin 4 (MUC4) Glycopeptide and Uses Thereof

Compositions and methods for immunotherapy

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen recognizing receptor and one of a chimeric costimulatory receptor. Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Modified erythrocyte precursor cells and uses thereof

Provided herein are modified erythrocyte precursor cells, erythrocytes generated from modified erythrocyte precursor cells, and uses thereof NYI-4507693vl ...

Xenoantigen-displaying anti-cancer vaccines and method of making

Compositions, methods of making, and methods of using, xenoantigen-displaying anticancer vaccines are described. In another broad aspect, there is provided herein a method of synthesizing an alkynefunctionalized composition of claim 1, comprising: deprotecting an ester comprising a Fmoc moiety to form a free acid; coupling the free acid of step (a) with an amine; and, removing the Fmoc moiety, and coupling the remaining moiety with palmitic acid to yield an alkyne-functionalized composition.

Potentiating antibody-induced complement-mediated cytotoxicity via PI3K inhibition

Methodologies and technologies for potentiating antibody-based cancer treatments by increasing complement-mediated cell cytotoxicity are disclosed. Further provided are methodologies and technologies for overcoming ineffective treatments correlated with and/or caused by sub-lytic levels of complement-activating monoclonal antibodies ("mAb") against cancer antigens or cancer antigens with low tumor cell density. While detectable levels of passively administered or vaccine-induced mAb against some antigens are able to delay or prevent tumor growth, low levels of mAb induce sublytic levels of complement activation and accelerate tumor growth. This complement-mediated accelerated tumor growth initiated by low mAb levels results in activation of the PI3K/AKT survival pathway. Methodologies and technologies relating to administration of PI3K inhibitors to overcome low dose mAb-initiated, complement-mediated PI3K activation and accelerated tumor growth are disclosed.

Composition comprising a complexed (m)RNA and a naked mRNA for providing or enhancing an immunostimulatory response in a mammal and uses thereof

Compositions and methods for generating an immune response to a tumor associated antigen

The compositions and methods are described for generating an immune response to a tumor associated antigen such as MUC1. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a neoplasm expressing the tumor associated antigen in the subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat neoplasms and associated diseases.

Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy

The invention covers the use of certain classes of lipids including cationic lipids in ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST OVARIAN CANCER AND OTHER CANCERS

Abstract The present invention relates to peptides, proteins, 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 tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST LUNG CANCER, INCLUDING NSCLC AND OTHER CANCERS

Abstract The present invention relates to peptides, proteins, 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 tumor associated T-cell peptide epitopes, alone or in combination with other tumor associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Modified gp100 and uses thereof

VACCINE NANOTECHNOLOGY

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

CAR T CELL THERAPIES WITH ENHANCED EFFICACY

The invention provides compositions and methods improved CAR T cell therapies. Specifically, the invention provides cells with reduced Tet, e.g., Tet2 function or expression, and methods of use therefore. The invention further provides Tet2 inhibitors and methods of use therefore in connection with CAR T cells.

METHODS OF PREPARING T CELLS FOR T CELL THERAPY

Provided herein are methods for delaying or inhibiting T cell maturation or differentiation in vitro for a T cell therapy, comprising contacting one or more T cells from a subject in need of a T cell therapy with an AKT inhibitor and at least one of exogenous Interleukin-7 (IL-7) and exogenous Interleukin-15 (IL-15), wherein the resulting T cells exhibit delayed maturation or differentiation. In some embodiments, the method further comprises administering the one or more T cells to a subject in need of a T cell therapy.

BRACHYURY DELETION MUTANTS, NON-YEAST VECTORS ENCODING BRACHYURY DELETION MUTANTS, AND THEIR USE

The invention provides Brachyury deletion mutant polypeptides, nucleic acids encoding the polypeptides, non-yeast vectors comprising the nucleic acids, non-yeast cells, and methods of use.

ANTIBODY AGAINST MUCIN 4 (MUC4) GLYCOPEPTIDE AND USE THEREOF

The present invention provides: an antibody that has specificity for MUC 4 having a sugar chain structure that is expressed at a high level in cancer cells; a glycopeptide that constitutes an antigen that is suitable for producing this antibody; and a new means and method for the diagnosis, prevention, and/or treatment of cancer by means of the aforementioned antibody. The present invention relates to a monoclonal antibody against a glycopeptide. The glycopeptide comprises a human MUC 4 tandem unit peptide having an amino acid sequence represented by SEQ ID NO: 1, and an O-linked sugar chain. The O-linked sugar chain is N-acetylgalactosamine (GalNAc) and binds to threonine, which is the 8th amino acid of the tandem unit peptide. The present invention further includes: a glycopeptide for use in the production of a monoclonal antibody against human MUC 4; a method for detecting MUC 4 in a human body fluid sample; a kit that includes the abovementioned monoclonal antibody; and a pharmaceutical ...

COMBINATION THERAPY FOR TREATING CANCER WITH A POXVIRUS EXPRESSING A TUMOR ANTIGEN AND AN ANTAGONIST AND/OR AGONIST OF AN IMMUNE CHECKPOINT INHIBITOR

The present disclosure encompasses therapies, compositions, and methods for treatment of a human cancer patient using a recombinant poxvirus encoding a tumor-associated antigen in combination with one or more agonists or antagonists of immune checkpoint inhibitors.

NANOPARTICLES FOR IMMUNOTHERAPY

Nanoparticles that activate complement in the absence of biological molecules are described. The nanoparticles are shown to specifically target antigen presenting cells in specifically in lymph nodes, without the use of a biological molecule for targeting. These particles are useful vehicles for delivering immunotherapeutics. Surface chemistries and chemical formulations for the nanoparticles are described.

COMPOSITION COMPRISING A COMPLEXED (M)RNA AND A NAKED MRNA FOR PROVIDING OR ENHANCING AN IMMUNOSTIMULATORY RESPONSE IN A MAMMAL AND USES THEREOF

The present invention relates to an immunostimulatory composition comprising a) an adjuvant component, comprising or consisting of at least one (m)RNA, complexed with a cationic or polycationic compound, and b) at least one free mRNA, encoding at least one therapeutically active protein, antigen, allergen and/or antibody, wherein the immunostimulatory composition is capable to elicit or enhance an innate and optionally an adaptive immune response in a mammal. The inventive immunostimulatory composition may be a pharmaceutical composition or a vaccine. The invention furthermore relates to a method of preparation of the inventive immunostimulatory composition. The invention also relates to the use of the inventive immunostimulatory composition or its components (for the preparation of a pharmaceutical composition or a vaccine) for the treatment of various diseases. Finally, the invention relates to kits containing the inventive immunostimulatory composition, its components and/or the pharmaceutical ...

MEMBRANE-BOUND CYTOKINE COMPOSITIONS AND METHODS OF MODULATING AN IMMUNE RESPONSE USING SAME

The present invention provides a cellular vaccine having a membrane-bound fusion protein that includes a non-antibody immunomodulatory molecule operatively fused to a heterologous membrane attachment domain. Non-antibody immunomodulatory molecules useful in the invention include immunostimulatory and immunosuppressive molecules such as cytokines. In one embodiment, the invention provides a cellular vaccine having a membrane-bound fusion protein that includes a non-antibody immunomodulatory molecule operatively fused to a heterologous membrane attachment domain and, additionally, a diseaseassociated antigen or immunogenic epitope thereof. Further provided by the invention are methods of modulating an immune response against a diseaseassociated antigen by administering to an individual a cellular vaccine having a membrane-bound fusion protein that includes a non-antibody immunomodulatory molecule operatively fused to a heterologous membrane attachment domain.

Compositions and methods HER2/NEU for tumor vaccine vaccination and immunotherapy involving a patient

COMMON LIGHT CHAINS AND METHODS OF USE

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST LUNG CANCER, INCLUDING NSCLC AND OTHER CANCERS

IMMUNE RESPONSE

Immune responses to a targeted antigen are increased in patients for treating human disease, by administering an immunogenic composition, wherein such patients are selected from a patient population of interest.

IMMUNOSTIMULATORY COMPOSITIONS, PARTICLES, AND USES RELATED THERETO

In some embodiments, described herein is a method of tumor treatment or tumor vaccination. The method generally comprises applying to a human being in need thereof a tumor therapeutic composition or tumor vaccine defined herein. The tumor therapeutic composition or tumor vaccine can be produced by protein transfer of glycosyl-phosphatidylinositol (GPI)-anchored immunostimulatory or costimulatory molecules.

COMPOSITION AND VACCINE FOR TREATING PROSTATE CANCER

The present invention relates to a composition comprising at least one mRNA encoding a combination of antigens capable of eliciting an (adaptive) immune response in a mammal, wherein the antigens are selected from the group consisting of PSA (Prostate-Specific Antigen), PSMA (Prostate-Specific Membrane Antigen), PSCA (Prostate Stem Cell Antigen), STEAP (Six Transmembrane Epithelial Antigen of the Prostate), MUC1 (Mucin 1) and PAP (Prostatic acid phosphatase). The invention furthermore relates to a vaccine comprising at least one mRNA encoding such a combination of antigens and to the use of said composition (for the preparation of a vaccine) and/or of the vaccine for eliciting an (adaptive) immune response for the treatment of prostate cancer (PCa), preferably of prostate adenocarcinoma, locally limited, locally advanced, metastatic, castration-resistant (hormone-refractory), metastatic castration-resistant and non-metastatic castration-resistant prostate cancers, and diseases or disorders ...

ONCOLOGY VACCINE

A pharmaceutical composition comprising at least two peptides of from 20 to 60 amino acids in length, selected from peptides comprising a sequence of at least 20 contiguous amino acids of one of the sequences shown in SEQ ID NOs: 1 to 40 and 48 or of a sequence having at least 80% identity to one of the sequences shown in SEQ ID NOs: 1 to 40 and 48, wherein each peptide comprises at least one CD8+ T-cell epitope and/or at least one CD4+ T-cell epitope.

Xenoantigen-displaying anti-cancer vaccines and method of making

Compositions, methods of making, and methods of using, xenoantigen-displaying anti-cancer vaccines are described.

CANCER VACCINE COMPOSITIONS AND METHODS FOR USE THEREOF

The compositions and methods are described for generating an immune response to a tumor associated antigen (TAA) such as MUC-1, survivin, cyclin B1, HBV, or HPV. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to the tumor associated antigen in the subject to which the vector is administered and optionally, boosting the immune response by administering a tumor associated antigen. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat neoplasms and associated diseases.

MULTIMERIC T-CELL MODULATORY POLYPEPTIDES AND METHODS OF USE THEREOF

НОВЫЕ ПЕПТИДЫ И КОМБИНАЦИИ ПЕПТИДОВ ДЛЯ ПРИМЕНЕНИЯ В ИММУНОТЕРАПИИ РАКА ЛЕГКИХ, В ТОМ ЧИСЛЕ НЕМЕЛКОКЛЕТОЧНОГО РАКА ЛЕГКИХ (НМРЛ) И ДРУГИХ ВИДОВ РАКА

Изобретение относится к биотехнологии. Описан пептид, который связывается с молекулой(ами) главного комплекса гистосовместимости (МНС), выбранный из группы: (а) пептид, состоящий из аминокислотной последовательности в соответствии с SEQ ID NO: 30, необязательно удлиненной на 1 аминокислоту на его N- и/или С-концевом участке; (б) пептид в соответствии с (а), где указанный пептид включает непептидные связи. Также описаны слитый пептид, набор и фармацевтическая композиция, содержащие описанный пептид. Раскрыты соответствующие описанному пептиду нуклеиновая кислота, вектор, клетка-хозяин. Изобретение расширяет арсенал средств для лечения рака. 11 н. и 9 з.п. ф-лы, 6 ил., 27 табл., 6 пр.

СПОСОБЫ ПОВЫШЕНИЯ ЭФФЕКТИВНОСТИ ПРОТИВООПУХОЛЕВОГО ИММУННОГО ОТВЕТА

Группа изобретений относится к медицине, а именно, к онкологии и может быть использована для повышения противоопухолевого иммунного ответа. Способы по изобретению включают введение антитела или его антиген-связывающего фрагмента, являющихся агонистами OX40, 1-метилтриптофана (1-MT) и иммуногенной композиции, содержащей опухолевый антиген, где указанный опухолевый антиген представляет собой антиген HPV. Использование изобретений позволяет добиться регрессии опухоли за счет синергетического эффекта комбинации путем индукции иммунного ответа на опухолевый антиген и увеличения соотношения CD8T-клеток и регуляторных T-клеток в опухоли. 5 н. и 20 з.п. ф-лы, 5 ил., 5 пр.

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ КОМПЛЕКС ПОЛИМЕРНОГО НОСИТЕЛЯ И ПЕРЕНОСИМОГО ВЕЩЕСТВА И ПО МЕНЬШЕЙ МЕРЕ ОДИН БЕЛКОВЫЙ ИЛИ ПЕПТИДНЫЙ АНТИГЕН

Группа изобретений относится к медицине и касается фармацевтической композиции для вакцинации против инфекционной болезни, аллергии или аллергического заболевания, аутоиммунного заболевания, или рака или опухолевого заболевания, содержащей комплекс полимерного носителя и переносимого вещества, по меньшей мере один белковый или пептидный антиген. Группа изобретений также касается набора для вакцинации против инфекционной болезни, аллергии или аллергического заболевания, аутоиммунного заболевания, или рака, или опухолевого заболевания; применения указанной фармацевтической композиции в качестве вакцины. Группа изобретений обеспечивает увеличение иммунного ответа против пептида или белка. 4 н. и 9 з.п. ф-лы, 16 пр., 30 ил., 1 табл.

КОМПОЗИЦИИ И СПОСОБЫ ДЛЯ БУСТИНГА ЭФФЕКТИВНОСТИ АДОПТИВНОЙ КЛЕТОЧНОЙ ИММУНОТЕРАПИИ

Группа изобретений относится к медицине и касается способа улучшения адоптивной клеточной иммунотерапии, включающего (a) введение субъекту эффективного количества популяции модифицированных Т-клеток человека, содержащих молекулу нуклеиновой кислоты, которая кодирует экзогенный антигенсвязывающий белок, при этом указанный антигенсвязывающий белок содержит гидрофобную часть, расположенную между внеклеточным связывающим компонентом и внутриклеточным эффекторным компонентом; и (b) введение субъекту эффективного количества популяции модифицированных гемопоэтических клеток-предшественников человека, модифицированных клеток иммунной системы человека или их комбинации, содержащих молекулу нуклеиновой кислоты, которая кодирует указанный антиген. Группа изобретений также касается способа лечения заболевания, ассоциированного с экспрессией антигена у субъекта, включающего стадии обеспечения улучшенной адоптивной клеточной иммунотерапии; композиции адоптивной клеточной иммунотерапии, содержащей (i) ...

НУКЛЕИНОВАЯ КИСЛОТА, СОДЕРЖАЩАЯ ИЛИ КОДИРУЮЩАЯ ГИСТОНОВУЮ СТРУКТУРУ ТИПА "СТЕБЕЛЬ-ПЕТЛЯ" И ПОЛИ(A)-ПОСЛЕДОВАТЕЛЬНОСТЬ ИЛИ СИГНАЛ ПОЛИАДЕНИЛИРОВАНИЯ, ДЛЯ УВЕЛИЧЕНИЯ ЭКСПРЕССИИ КОДИРУЕМОГО ОПУХОЛЕВОГО АНТИГЕНА

Изобретение относится к биотехнологии. Предложен набор, композиция, применение и способ для лечения опухолевых заболеваний. Изобретение может быть использовано в медицине. 7 н. и 20 з.п. ф-лы, 15 табл., 27 ил.

ПРОТИВОРАКОВЫЕ ВАКЦИНЫ, НАПРАВЛЕННЫЕ НА MUC16, И ИХ ПРИМЕНЕНИЕ

Изобретение относится к биотехнологии. Раскрыты молекулы нуклеиновой кислоты, содержащие одну или более последовательностей нуклеиновой кислоты, которые кодируют модифицированный консенсусный антиген MUC16. Описаны векторы, композиции и вакцины, содержащие одну или более последовательностей нуклеиновых кислот, которые кодируют модифицированный консенсусный антиген MUC16. Раскрыты способы лечения субъекта с опухолью, экспрессирующей MUC16, и способы предотвращения опухоли, экспрессирующей MUC16. Раскрыт модифицированный консенсусный антиген MUC16. Изобретение позволяет получение безопасных и эффективных вакцин, которые применимы к опухолям, экспрессирующим MUC16, обеспечивая тем самым лечение и способствуя выживанию субъектов, пораженных такими видами рака. 27 н.п. ф-лы, 28 табл., 6 пр., 54 ил.

СПОСОБЫ ПОВЫШЕНИЯ ЭФФЕКТИВНОСТИ ПРОТИВООПУХОЛЕВОГО ИММУННОГО ОТВЕТА

КОМПОЗИЦИИ И СПОСОБЫ ИММУНОТЕРАПИИ

ИММУНОТЕРАПЕВТИЧЕСКИЕ КОМПОЗИЦИИ НА ОСНОВЕ ДРОЖЖЕЙ-MUC1 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

АНТИГЕН MUC1 СО СНИЖЕННЫМ ЧИСЛОМ ПОВТОРЯЮЩИХСЯ VNTR-БЛОКОВ

... 1. Молекула нуклеиновой кислоты, кодирующая антиген MUC1, причем указанная молекула способна вызывать иммунный ответ in vivo и имеет сниженную подверженность рекомбинации при сравнении с полноразмерным MUC1. 2. Молекула нуклеиновой кислоты, кодирующая антиген MUC1, содержащий от 1 до 15 полностью повторяющихся VNTR-блоков. 3. Молекула нуклеиновой кислоты по п.2, содержащая менее чем 8 полностью повторяющихся VNTR-блоков. 4. Молекула нуклеиновой кислоты по п.1 или 2, где по меньшей мере один VNTR мутирован для снижения потенциала гликозилирования. 5. Молекула нуклеиновой кислоты по п.1 или 2, которая включает в себя последовательности, кодирующие эпитоп, выбранный из группы: FLSFHISNL, NSSLEDPSTDYYQELQRDISE и NLTISDVSV. 6. Молекула нуклеиновой кислоты по пп.1 или 2, где эта молекула представляет собой молекулу ДНК. 7. Плазмида, содержащая молекулу ДНК по п.6. 8. Протеин, кодируемый нуклеиновой кислотой по любому из пп.1-6. 9. Фармацевтическая композиция, содержащая нуклеиновую кислоту по ...

CAR constructs

Modified plant viruses

STABILIZED MRNA WITH INCREASED G/C CONTENT AND OPTIMIZED CODON USAGE FOR THE GENE THERAPY

MUCINPEPTID WITH IMMUNE-STRENGTHENING CHARACTERISTICS

MODIFIED GP100 AND ITS USE

SYNTHETIC GLYKOLIPOPEPTIDE AS VACCINES

STANDS TO ZELLTRANSPLANTATION

STABILIZED TUMORANTIGEN MRNA WITH INCREASED ONE G/CGEHALT

Complex of a protein comprising zinc oxide-binding peptides and zinc oxide nanoparticles, and use thereof

The present invention relates to a complex of a protein comprising zinc oxide-binding peptides and zinc oxide nanoparticles, to the use thereof as a drug delivery carrier for manufacturing medicines, and to a vaccine composition and a contrast agent comprising the composite. The protein comprising zinc oxide-binding peptides significantly improves the in vivo availability of zinc oxide-binding peptides, and therefore the complex of the present invention can be used not only as a drug delivery carrier for in vivo drug delivery or intracellular drug delivery, but also for in vivo imaging or cell imaging. The complex can be used for producing separating agents for effectively separating biological materials, therapeutic agents for hyperthermia, etc., contrast agents for MRI, and beads applicable to biosensors.

Packaging of Immunostimulatory Substances into Virus-Like Particles: Method of Preparation and Use

The invention relates to the finding that virus like particles (VLPs) can be loaded with immunostimulatory substances, in particular with DNA oligonucleotides containing non-methylated C and G (CpGs). Such CpG-VLPs are dramatically more immunogenic than their CpG-free counterparts and induce enhanced B and T cell responses. The immune response against antigens optionally coupled, fused or attached otherwise to the VLPs is similarly enhanced as the immune response against the VLP itself. In addition, the T cell responses against both the VLPs and antigens are especially directed to the Th1 type. Antigens attached to CpG-loaded VLPs may therefore be ideal vaccines for prophylactic or therapeutic vaccination against allergies, tumors and other self-molecules and chronic viral diseases.

Recombinant tumor vaccine and method of producing such vaccine

The present disclosure provides tumor vaccines useful for preventing and treating tumors and cancers. The tumor vaccines may contain nucleic acids encoding for antigen presenting peptides, cytokines and other factors useful for preventing and treating tumors and cancers, or expression vectors or viruses containing such nucleic acids, or host cells containing such nucleic acids or expression vectors.

Dendritic Cells Loaded With Heat Shocked Melanoma Cell Bodies

The present invention includes compositions and methods for the isolation, purification and preparation of immunogenic antigens for the production of customized cancer vaccines that include dendritic cells that are contacted with an antigen that includes heat-shocked cancer cells.

Immunotherapy of cancer using genetically engineered gd2-specific t cells

The present invention concerns immunotherapy for cancers having cells that comprise the ganglioside GD2 antigen. In specific embodiment, T cells having a chimeric receptor that targets GD2 is employed. In particular cases, the chimeric receptor comprises antibody, cytoplasmic signaling domain from the T cell receptor, and/or costimulatory molecule(s).

Polyvalent conjugate vaccine for cancer

This invention provides a polyvalent vaccine comprising at least two conjugated antigens selected from a group containing glycolipid antigen, polysaccharide antigen, mucin antigen, glycosylated mucin antigen and an appropriate adjuvant. This invention also provides a multivalent vaccine comprising at least two of the following: glycosylated MUC-1-32mer, Globo H, GM2, Le y , Tn(c), sTN(c), and TF(c). This invention provides the vaccine above, wherein the adjuvant is saponin-based adjuvant. This invention provides a method for inducing immune response in a subject comprising administering an effective amount of the vaccine above to the subject. Finally, this invention provides a method for treating cancer in a subject comprising administering an appropriate amount of the vaccine above to the subject.

Parapoxvirus vectors

The present invention is in the field of viral immunotherapy. The invention provides new pseudocowpox (PCPV) viruses, in particular recombinant PCPV, composition thereof as well as their therapeutic use for preventing or treating diseases, and, notably, proliferative diseases like cancers and restenosis and infectious diseases such as chronic ones. The present invention also provides methods for generating and amplifying such a PCPV and a method for eliciting or stimulating and/or re-orienting an immune response using such a PCPV. More specifically, the invention provides an alternative to the existing poxvirus vectors such as MVA (Modified Virus Ankara) and may be largely used for the therapeutic vaccination. 1. A pseudocowpoxvirus (PCPV) wherein said PCPV comprises at least one foreign nucleic acid inserted in its genome.2. The PCPV of claim 1 , wherein said PCPV is obtained from the wild-type TJS strain as identified by ATCC reference number ATCC VR-634™ or from a virus strain of the same or similar name or functional fragments and variants thereof.3. The PCPV of claim 1 , wherein said PCPV is further defective for a viral function encoded by the PCPV genome.4. The PCPV of claim 1 , wherein said foreign nucleic acid encodes a polypeptide selected from the group consisting of polypeptides that compensate for defective or deficient proteins in a subject claim 1 , suicide gene products claim 1 , armed gene products claim 1 , immunostimulatory polypeptides claim 1 , and antigenic polypeptides.5. The PCPV of claim 4 , wherein said immunostimulatory polypeptide is selected from the group consisting of cytokines claim 4 , chemokines claim 4 , interferons claim 4 , tumor necrosis factor claim 4 , colony-stimulating factors claim 4 , APC-exposed proteins claim 4 , agonists of immune checkpoints claim 4 , and antagonists of immune checkpoints.6. The PCPV of claim 5 , wherein said immunostimulatory polypeptide is GM-CSF or is an agonist OX40-directed antibody.7. The PCPV of ...

PHARMACEUTICAL COMPOSITION FOR USE IN THE TREATMENT OF CANCER

The present invention relates to an antigen composition comprising at least one mesothelioma cancer cell associated antigen and a pharmaceutically acceptable carrier for use in the treatment of cancer, in particular mesothelioma, wherein dendritic cells are loaded with said antigen composition and wherein said loaded dendritic cells are administered in combination with one or more checkpoint inhibitors, to patients. The present invention also relates to an antigen composition comprising at least two mesothelioma cancer cell associated antigens and a pharmaceutically acceptable carrier. The present invention further relates to an antigen composition comprising at least two mesothelioma cancer cell associated antigens and a pharmaceutically acceptable carrier, for use as a pharmaceutical, in particular for use in the treatment of mesothelioma. 1. An antigen composition comprising at least one mesothelioma cancer cell associated antigen and a pharmaceutically acceptable carrier for use in the treatment of cancer , wherein dendritic cells are loaded with said antigen composition and are administered to patients in need thereof together with one or more checkpoint inhibitors.2. Antigen composition for use according to claim 1 , wherein the one or more checkpoint inhibitors inhibit a checkpoint protein selected from the group of: TIM3 claim 1 , CTLA4 claim 1 , PD1 claim 1 , PDL1 claim 1 , PDL2 claim 1 , LAG3 claim 1 , CD137 claim 1 , CD40 claim 1 , OX40 claim 1 , VISTA claim 1 , CD112R and BTLA claim 1 , preferably TIM3 claim 1 , CTLA4 claim 1 , PD1 claim 1 , PDL1 claim 1 , PDL2 and LAG3 claim 1 , more preferably PD1 and PDL13. Antigen composition for use according to any of the previous claims claim 1 , wherein the checkpoint inhibitor is chosen from: atezolizumab claim 1 , avelumab claim 1 , durvalumab claim 1 , nivolumab and pembrolizumab claim 1 , preferably nivolumab.4. Antigen composition for use according to any of the previous claims claim 1 , wherein the one or ...

Anti-hsp70 specific chimeric antigen receptors (cars) for cancer immunotherapy

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from an anti-HSP70 monoclonal antibody, conferring specific immunity against HSP70 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating in particular leukemia.

METHODS AND VACCINES FOR INDUCING IMMUNE RESPONSES TO MULTIPLE DIFFERENT MHC MOLECULES

This document provides methods and materials relating to isolated polypeptides, polypeptide preparations, vaccine preparations (e.g., anti-cancer vaccine preparations), and methods for vaccinating mammals. For example, polypeptides (e.g., CMV, MUC1, HER2, Mesothelin (MESO), TRAG-3, or CALR polypeptides) having the ability to be processed into different polypeptides such that the processed polypeptides as a group are capable of being presented by different MHC molecules present in a particular mammalian population are provided. 12-. (canceled)3. A composition comprising at least one isolated polypeptide selected from the group consisting of SEQ ID NOs:1-58.4. The composition of claim 3 , wherein said polypeptide is amidated at the C-terminus and/or acetylated at the N-terminus.5. The composition of claim 3 , wherein said composition further comprises an adjuvant.6. A method of treating a mammal having cancer or a precancerous condition claim 3 , wherein said method comprises administering to said mammal a composition comprising an adjuvant and at least one polypeptide claim 3 , wherein the amino acid sequence of said polypeptide is as set forth in any one of SEQ ID NOs:1-58.7. The method of claim 6 , wherein said mammal is a human.8. The method of claim 6 , wherein said cancer is breast cancer claim 6 , pancreatic cancer claim 6 , ovarian cancer claim 6 , stomach cancer claim 6 , lung cancer claim 6 , colon cancer claim 6 , multiple myeloma claim 6 , leukemia claim 6 , brain cancer claim 6 , or melanoma cancer.9. The method of wherein said precancerous condition is primary myelofibrosis) claim 6 , essential thrombocythemia claim 6 , or polycythemia vera.10. The method of claim 6 , wherein said adjuvant is CpG claim 6 , aluminum sulfate claim 6 , aluminum phosphate claim 6 , MF59 claim 6 , Pam3CSK4 claim 6 , LPS claim 6 , polylC claim 6 , imiquimod claim 6 , or R848.11. The method of claim 6 , wherein said polypeptide is amidated at the C-terminus and/or acetylated at ...

Cll1-specific multi-chain chimeric antigen receptor

The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs, which are made specific to the antigen CLL1. Such CARs aim to redirect immune cell specificity and reactivity toward malignant cells expressing the tumor antigen CLL1. The alpha, beta and gamma polypeptides composing these CARs are designed to assemble in juxtamembrane position, which forms flexible architecture closer to natural receptors, that confers optimal signal transduction. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer, especially leukemia.

Hla-a24 agonist epitopes of muc1-c oncoprotein and compositions and methods of use

The invention provides a human cytotoxic T lymphocyte (CTL) agonist epitope from the C-terminal subunit of mucin 1 (MUC1-C), which can be used as a peptide, polypeptide (protein), and/or in vaccine or other composition for the prevention or therapy of cancer. The invention further provides a nucleic acid encoding the peptide, protein, or polypeptide, a vector comprising the nucleic acid, a cell comprising the peptide, polypeptide, nucleic acid, or vector, and compositions thereof.

DE NOVO BINDING DOMAIN CONTAINING POLYPEPTIDES AND USES THEREOF

Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications. 149-. (canceled)50. A method for purifying a target of interest comprising:(a) contacting a sample comprising a target of interest with a composition comprising a polypeptide agent attached to a solid support under conditions that permit binding of the composition to the target of interest; and(b) removing a portion of the sample that is not bound to the composition,wherein the polypeptide agent has an amino acid sequence selected from the group consisting of SEQ ID NO: 12-183.51. The method of claim 50 , wherein the solid support comprises a bead claim 50 , and the composition is suitable for use in affinity chromatography to purify the target of interest.52. The method of claim 50 , wherein the target of interest can be eluted from the composition.53. The method of claim 50 , wherein a nucleic acid molecule encoding the polypeptide is packaged in an expression vector that is used to transduce a cell line to cause the cell line to express the polypeptide.54. The method of claim 50 , wherein the polypeptide agent is attached to the solid support through non-covalent association.55. The method of claim 50 , wherein the polypeptide agent is attached to the solid support through covalent bonding.56. The method of claim 50 , wherein the polypeptide agent of the composition further comprises a peptide tag claim 50 , wherein the peptide tag comprises a hexahistidine moiety or a FLAG tag.57. The method of claim 50 , wherein the ...

METHODS OF TREATING HEMATOLOGICAL DISORDERS, SOLID TUMORS, OR INFECTIOUS DISEASES USING NATURAL KILLER CELLS

Provided herein are methods of treating a hematological disorder, a solid tumor, or an infectious disease in a subject in need thereof using natural killer cells in combination with a second agent, or using natural killer cells with genetic modifications for target specificity and/or homing specificity. 182.-. (canceled)83. A method of treating a viral infection in a subject in need thereof , comprising administering to said subject an isolated population of NK cells or a pharmaceutical composition thereof , wherein the NK cells comprise a chimeric antigen receptor (CAR) , wherein said CAR comprises an extracellular domain that binds to an antigen on an infected cell , a transmembrane domain , and an intracellular stimulatory domain that comprises a co-stimulatory domain comprising the intracellular domain of NKp46 , NKp44 , NKp30 , DAP10 or DAP12.84. (canceled)85. The method of claim 83 , wherein the NK cells comprising the CAR are derived from CD34+ hematopoietic stem cells (HSCs) that are engineered to express the CAR.86. The method of claim 83 , wherein the extracellular domain that binds to an antigen on an infected cell is a viral antigen binding domain.87. The method of claim 83 , wherein the extracellular domain that binds to an antigen on an infected cell is an scFv domain.88. The method of claim 83 , wherein the intracellular stimulatory domain is a CD3 zeta signaling domain.89. (canceled)90. The method of claim 83 , wherein the NK cells further comprise a homing receptor.91. The method of claim 90 , wherein the NK cells comprising the homing receptor are derived from CD34+ hematopoietic stem cells (HSCs) that are engineered to express the homing receptor.92. The method of claim 90 , wherein the homing receptor is CXCR4 claim 90 , VEGFR2 claim 90 , or CCR7.93103.-. (canceled)104. The method of claim 83 , wherein the step of administering to said subject an isolated population of NK cells or a pharmaceutical composition thereof is by injection claim 83 , ...

COMPOSITIONS AND METHODS FOR T CELL DELIVERY OF THERAPEUTIC MOLECULES

The present invention includes compositions and methods for modifying a T cell with a nucleic acid encoding a switch molecule comprising an extracellular domain comprising a membrane receptor or fragment thereof and an intracellular domain comprising a signaling receptor or fragment thereof. In one aspect, a method comprises introducing a nucleic acid encoding a switch molecule and a nucleic acid encoding a soluble fusion protein and/or a nucleic acid encoding a bispecific antibody into a population of cells comprising T cells, wherein the T cells transiently expresses the switch molecule and soluble fusion protein or bispecific antibody. In other aspect, compositions of T cells and methods of treating a disease or condition, such as cancer or an autoimmune disease, are also included. 170-. (canceled)71. A method of treating a disease or condition , the method comprising administering to a subject a composition comprising a population of modified T cells comprising a nucleic acid sequence encoding a switch molecule , wherein the switch molecule comprises:(a) an extracellular domain comprising a membrane receptor or fragment thereof selected from the group consisting of a transforming growth factor-beta receptor (TGF-beta-R), programmed cell death 1 (PD1) receptor, programmed cell death ligand 1 (PDL1) receptor, interferon-gamma receptor (IFN-gamma) receptor, and any combination thereof; and(b) an intracellular domain comprising a signaling receptor or fragment thereof, wherein the signaling receptor is selected from the group consisting of interleukin-12 receptor (IL-12R), CD3, CD28, CD137, CD27, ICOS, OX40, and any combination thereof; andwherein the T cells express the switch molecule and interaction of the extracellular domain of the switch molecule with its respective ligand induces the T cells to secrete an activation factor at a target site, thereby treating the disease or condition.72. The method according to claim 71 , wherein the membrane receptor is TGF- ...

NUCLEIC ACID MOLECULES ENCODING FOR CHIMERIC CSPG4 PROTEINS AND THERAPEUTIC USES THEREOF

A nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan 4 (CSPG4) protein, wherein the chimeric CSPG4 protein comprises, from the N-terminal to the C-terminal: i) a first portion derived from the human CSPG4 sequence and a second portion derived from the canine CSPG4 sequence or ii) a first portion derived from the canine CSPG4 sequence and a second portion derived from the human CSPG4 sequence. 1. Nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan-4 (CSPG4) protein , wherein the chimeric CSPG4 protein comprises , from the N-terminus to the C-terminus:i) a first portion derived from the human sequence of CSPG4 and a second portion derived from the canine sequence of CSPG4, orii) a first portion derived from the canine sequence of CSPG4 and a second portion derived from the human sequence of CSPG4.4. Nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan-4 (CSPG4) protein according to for use as a medicament.5. Nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan-4 (CSPG4) protein for use according to claim 4 , for the treatment and/or prevention of CSPG-4 positive neoplasia in a mammal claim 4 , preferably a dog or a human claim 4 , more preferably a dog.6. Nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan-4 (CSPG4) protein for use according to claim 4 , wherein the nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan-4 (CSPG4) protein is part of a plasmid.7. Pharmaceutical composition comprising at least one nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan-4 (CSPG4) protein according to and a pharmaceutically acceptable excipient and/or vehicle.8. Pharmaceutical composition according to claim 7 , wherein the composition is formulated in the form of a DNA vaccine.9. Pharmaceutical composition according to claim 7 , comprising an adjuvant to stimulate an immune response.10. Use of a nucleic acid molecule ...

Effective generation of tumor-targeted t cells derived from pluripotent stem cells

The present invention relates to the field of adoptive immunotherapy. The invention provides methods for generating phenotypically defined, functional, and/or expandable T cells from pluripotent stem cells engineered through safe genetic modifications. The engineered cells may provide one or more of: 1) targeting a specific predetermined antigen expressed on the cell surface of a target cell in an HLA independent manner, 2) enhanced survival and functional potential 3) “off-the-shelf” T cells for administration to multiple recipients, eventually across immunogenic barriers, and/or 4) cytotoxic potential and anti-tumor activity.

Mucin antigen vaccine

Provided are expression vectors for generating an immune response to a mucin. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal, a mucin antigen and CD40 ligand. Also provided are methods of generating an immune response against cells expressing a mucin by administering an effective amount of the vector. Further provided are methods of generating an immune response against cancer cells expressing a mucin in an individual by administering an effective amount of the vector. Still further provided are methods of overcoming anergy to a mucin self antigen by administering an effective amount of the vector.

In Vivo Activation of Antigen Presenting Cells for Enhancement of Immune Responses Induced by Virus-Like Particles

The invention relates to the finding that stimulation of antigen presenting cell (APC) activation using substances such as anti-CD40 antibodies or DNA oligomers rich in non-methylated C and G (CpGs) can dramatically enhance the specific T cell response obtained after vaccination with recombinant virus like particles (VLPs) coupled, fused or otherwise attached to antigens. While vaccination with recombinant VLPs fused to a cytotoxic T cell (CTL) epitope of lymphocytic choriomeningitis virus induced low levels cytolytic activity only and did not induce efficient anti-viral protection, VLPs injected together with anti-CD40 antibodies or CpGs induced strong CTL activity and full anti-viral protection. Thus, stimulation of APC-activation through antigen presenting cell activators such as anti-CD40 antibodies or CpGs can exhibit a potent adjuvant effect for vaccination with VLPs coupled, fused or attached otherwise to antigens.

Combination Of The Application Of Antibodies For Immunostimulation Together With Glucocorticoids

The present invention relates to methods for reducing or eliminating the non-specific release of a cytokine associated with a disease comprising administering at least one glucocorticoid and an immunostimulating antibody. Additionally, the present invention relates to a pharmaceutical composition that contains at least one immunostimulating antibody and at least one glucocorticoid. 1. A method for reducing the non-specific release of a cytokine associated with a disease comprising administering at least one glucocorticoid and an immunostimulating antibody.2. The method of claim 1 , wherein the glucocorticoid is a synthetic glucocorticoid.3. The method of claim 2 , wherein the synthetic glucocorticoid is selected from the group consisting of prednisone claim 2 , prednisolone claim 2 , methylprednisolone claim 2 , triamcinolone claim 2 , betamethasone claim 2 , dexamethasone claim 2 , cortisone acetate claim 2 , prednylidene claim 2 , deflazacort claim 2 , cloprednol claim 2 , fluocortolone and budenoside.4. The method of claim 1 , wherein the disease is a cancerous disease.5. The method of claim 5 , wherein the cancerous disease is selected from the group consisting of gastric carcinoma claim 5 , adenocarcinoma claim 5 , malignant melanoma claim 5 , colonic carcinoma claim 5 , pancreatic carcinoma claim 5 , ovarian carcinoma claim 5 , uterine carcinoma claim 5 , hepatocellular carcinoma claim 5 , all histological types of bronchial carcinoma claim 5 , lymphomas claim 5 , sarcomas claim 5 , blastomas and gastrointestinal stromal tumour (GIST).6. The method of claim 1 , wherein the antibody is a monoclonal antibody claim 1 , a chimeric antibody claim 1 , humanized antibody claim 1 , human antibody claim 1 , trifunctional antibody claim 1 , multispecific antibody and/or multifunctional antibody.7. The method of claim 6 , wherein the multispecific antibody is a bispecific antibody which specifically recognizes a tumour antigen and a CD marker.8. The method of claim 7 , ...

AUGMENTATION OF PERSONALIZED TUMOR SPECIFIC ADAPTIVE IMMUNITY THROUGH EXTRACORPOREAL REMOVAL OF IMMUNE BLOCKING FACTORS

Disclosed are means, methods and compositions of matter useful for amplification of adaptive immune responses towards neoplastic tissue. In one embodiment, immunization of a patient is performed by a means comprising of administering either an exogenous vaccine or stimulation of immunogenicity of the tumor so as to cause release of antigens/increased exposure of antigens, thus resulting in an “endogenous” vaccine. Subsequent to vaccination a patient is treated by an immunopheresis procedure, in order to allow for removal of “blocking factors” produced by the tumor or produced by cells programmed by tumors to produce said blocking factors. In one embodiment further immunization is performed subsequent to removal of said blocking factors in order to allow for enhancement of adaptive immune responses 116-. (canceled)17. A method of stimulating an immune response against a tumor of a patient , comprising the steps of:(a) extracorporeally removing a soluble tumor necrosis factor-alpha receptor (sTNFalphaR) from the patient, thereby elevating infiltration of a lymphocyte into the tumor; and(b) administering a vaccine comprising Dendritic cells (DC) to the patient, thereby activating the lymphocyte and stimulating the immune response against the tumor.18. The method of claim 17 , wherein the lymphocyte is a T cell.19. The method of claim 18 , wherein the T cell is a CD8+ T cell.20. The method of claim 17 , wherein the DC expresses at least one of CD80 and CD86.21. The method of claim 17 , wherein the DC of step (b) is produced by:obtaining a DC from the patient prior to step (a) or (b); andpulsing the obtained DC ex vivo with an antigen associated with the tumor (TAA) prior to administering said vaccine to the patient.22. The method of claim 21 , wherein the step of obtaining the DC comprises the steps of:obtaining a DC progenitor from the patient; andculturing the DC progenitor in interleukin-4 and GM-CSF to induce differentiation into the DC.23. The method of claim 17 , ...

AUGMENTATION OF PERSONALIZED TUMOR SPECIFIC ADAPTIVE IMMUNITY THROUGH EXTRACORPOREAL REMOVAL OF IMMUNE BLOCKING FACTORS

Disclosed are means, methods and compositions of matter useful for amplification of adaptive immune responses towards neoplastic tissue. In one embodiment, immunization of a patient is performed by a means comprising of administering either an exogenous vaccine or stimulation of immunogenicity of the tumor so as to cause release of antigens/increased exposure of antigens, thus resulting in an “endogenous” vaccine. Subsequent to vaccination a patient is treated by an immunopheresis procedure, in order to allow for removal of “blocking factors” produced by the tumor or produced by cells programmed by tumors to produce said blocking factors. In one embodiment further immunization is performed subsequent to removal of said blocking factors in order to allow for enhancement of adaptive immune responses 116-. (canceled)17. A method of augmenting radiation therapy in treating a tumor or a patient , comprising the steps of:(a) performing radiation therapy on the patient; and(b) extracorporeally removing a soluble tumor necrosis factor-alpha receptor (sTNFalphaR) from the patient, thereby augmenting the radiation therapy.181. The method of claim , wherein:step (b) induces an increase in production of TNF-alpha by the patient; andstep (a) increases availability of TNF-alpha in the patient.191. The method of claim , further comprising administering a vaccine comprising dendritic cells (DC).203. The method of claim , wherein the DC are pulsed with a tumor-associated antigen (TAA) prior to administering to the patient.214. The method of claim , wherein the pulsing is performed ex vivo.224. The method of claim , wherein the TAA is derived from the tumor.234. The method of claim , wherein the TAA is selected from tumor-derived microvesicles in circulation.246. The method of claim , wherein the TAA is derived from the tumor by means of a biopsy.253. The method of claim , wherein the DC express at least one of CD80 and CD86.261. The method of claim , further comprising after step (b ...

Compositions and methods for delivery of biomacromolecule agents

The present invention relates to nanoparticles complexed with biomacromolecule agents configured for treating, preventing or ameliorating various types of disorders, and methods of synthesizing the same. In particular, the present invention is directed to compositions comprising nanoparticles (e.g., synthetic high density lipoprotein (sHDL)) carrying biomacromolecule agents (e.g., nucleic acid, peptides, glycolipids, etc.), methods for synthesizing such nanoparticles, as well as systems and methods utilizing such nanoparticles (e.g., in diagnostic and/or therapeutic settings).

Antibodies specific to muc18

Antibodies specific to MUC18 (a.k.a. MCAM or CD146) and uses thereof for therapeutic and diagnostic purposes are provided. Also provided herein are chimeric antigen receptors (CARs) comprising an extracellular antigen-binding fragment that binds MUC18 and immune cells expressing such.

Cancer treatment with 237 car-t cell based therapeutics recognizing the tn epitope

The disclosure provides Tn epitope-specific chimeric antigen receptors and scFvs, including soluble scFvs and multimeric scFvs, as well as methods of identifying cancer subjects and cancer subject sub-populations amenable to anti-Tn immunotherapy and methods of treating cancer.

INTRATUMORAL VACCINATION

The present disclosure relates to, inter alia, a method for treating a tumor by intratumorally delivering an effective amount of a composition comprising an expression vector that comprises a first nucleotide sequence encoding a secretable vaccine protein, and a second nucleotide sequence encoding a T cell costimulatory fusion protein. 1. A method for treating a tumor in a subject in need thereof , comprising intratumorally delivering an effective amount of a composition comprising an expression vector that comprises a first nucleotide sequence encoding a secretable vaccine protein , and a second nucleotide sequence encoding a T cell costimulatory fusion protein.2. The method of claim 1 , wherein the intratumoral delivery is in vivo by injection.3. The method of claim 2 , further comprising administering to the subject effective amount of a biological cell comprising an expression vector that comprises a first nucleotide sequence encoding a secretable vaccine protein claim 2 , and a second nucleotide sequence encoding a T cell costimulatory fusion protein claim 2 , wherein the T cell costimulatory fusion protein enhances activation of antigen-specific T cells when administered to the subject4. The method of any one of - claim 2 , wherein the method elicits a potent immune response in less-immunogenic tumors claim 2 , optional a tumor with reduced inflammation (“cold tumor”) relative to a responsive claim 2 , inflamed tumor (“hot tumor”).5. The method of any one of - claim 2 , wherein the method enhances CD4+/CD8+ T cell cross-priming to tumor neo-antigens.6. The method of any of the above claims claim 2 , wherein the vector is a mammalian expression vector.7. The method of any of the above claims claim 2 , wherein the vaccine protein is a secretable gp96-Ig fusion protein which optionally lacks the gp96 KDEL (SEQ ID NO:3) sequence.8. The method of claim 7 , wherein the Ig tag in the gp96-Ig fusion protein comprises the Fc region of human IgG1 claim 7 , IgG2 claim 7 ...

Mnd promoter chimeric antigen receptors

The invention provides vector compositions for delivering improved adoptive T cell therapies.

Medicine

The present invention provides a medicine comprising a Toll-like receptor agonist, LAG-3 protein, a variant or derivative thereof.

COMPOSITION COMPRISING A COMPLEXED (m)RNA AND A NAKED mRNA FOR PROVIDING OR ENHANCING AN IMMUNOSTIMULATORY RESPONSE IN A MAMMAL AND USES THEREOF

The present invention relates to an immunostimulatory composition comprising a) an adjuvant component, comprising or consisting of at least one (m)RNA, complexed with a cationic or polycationic compound, and b) at least one free mRNA, encoding at least one therapeutically active protein, antigen, allergen and/or antibody, wherein the immunostimulatory composition is capable to elicit or enhance an innate and optionally an adaptive immune response in a mammal. The inventive immunostimulatory composition may be a pharmaceutical composition or a vaccine. The invention furthermore relates to a method of preparation of the inventive immunostimulatory composition. The invention also relates to the use of the inventive immunostimulatory composition or its components (for the preparation of a pharmaceutical composition or a vaccine) for the treatment of various diseases. Finally, the invention relates to kits containing the inventive immunostimulatory composition, its components and/or the pharmaceutical composition or vaccine. 117-. (canceled)18. An immunostimulatory composition comprising:a) an adjuvant component, comprising at least one RNA, complexed with protamine wherein the weight ratio of the at least one mRNA to protamine in the adjuvant component is 2:1 to 3:1; andb) at least one free mRNA, encoding at least one antigen, wherein the molar ratio of the RNA of the adjuvant component to the at least one free mRNA of the second component b) is 1:1 to 1:4.19. A pharmaceutical composition claim 18 , comprising an immunostimulatory composition according to and optionally a pharmaceutically acceptable carrier claim 18 , adjuvant claim 18 , and/or vehicle.20. A method for preparing an immunostimulatory composition as defined according to claim 18 , comprising following steps: (i) preparing the adjuvant component by mixing in a specific ratio the at least one mRNA and the protamine; and (ii) preparing the immunostimulatory composition by adding in a specific ratio of the at ...

Human application of engineered chimeric antigen receptor (car) t-cells

The present invention concerns methods and compositions for immunotherapy employing a modified T cell comprising a chimeric antigen receptor (CAR). In particular aspects, CAR-expressing T-cells are producing using electroporation in conjunction with a transposon-based integration system to produce a population of CAR-expressing cells that require minimal ex vivo expansion or that can be directly administered to patients for disease (e.g., cancer) treatment.

ANTIGEN SPECIFIC MULTI EPITOPE VACCINES

The presently described subject matter relates to cancer vaccines composed of the signal peptide domain of tumor associated antigens or proteins. The described peptide vaccines have multiple MHC class I and class II epitopes which are highly abundant in the population. Therefore, these vaccines induce a strong, comprehensive immune response against the target proteins in the majority of the vaccinated population, and thereby induce an immune reaction against tumors expressing such target proteins. Specifically, the presently described subject matter relates to peptide vaccines composed of the signal peptide domain of Mucin (MUC1), BAGE-1 or ARMET, and their use for the treatment of cancers which express Mucin (MUC1), BAGE-1 or ARMET. 1. A method of enriching a T cell population in vitro , the method comprising: contacting said T cell population with a polypeptide comprising a signal peptide or derivative thereof , thereby obtaining an enriched T cell population responsive to said signal peptide or derivative thereof.2. The method of claim 1 , wherein said polypeptide consists of at most 50 amino acids.3. The method of claim 1 , wherein said polypeptide consists of at most 25 amino acids.4. The method of claim 1 , wherein said signal peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-39.5. The method of claim 1 , wherein said signal peptide is a MUC1 signal peptide.6. The method of claim 5 , wherein said MUC1 signal peptide or derivatives thereof comprise the amino acid sequence MTPGTQSPFFLLLLLTVLTVV (SEQ ID NO. 10).7. The method of claim 5 , wherein said MUC1 signal peptide or derivatives thereof comprise an amino acid sequence selected from the group consisting of SEQ ID NO: 29-39.8. The method of claim 5 , wherein said MUC1 signal peptide or derivatives thereof comprise an amino acid sequence selected from the group consisting of SEQ ID NO: 31-39.9. The method of claim 5 , wherein said MUC1 signal peptide or derivatives ...

High purity ovarian cancer stem cells for active autologous immune therapy

The disclosure provides cancer stem cells, for use in stimulating immune response against a cancer, such as ovarian carcinoma. Methods for preparing and purifying the cancer stem cells are provided.

Combination Immunotherapy Compositions Against Cancer and Methods

Disclosed are immunotherapeutic compositions and the concurrent use of combinations of such compositions for the improved induction of therapeutic immune responses and/or for the prevention, amelioration and/or treatment of disease, including, but not limited to, cancer and infectious disease. 178-. (canceled)79. A method to reduce tumor burden or inhibit tumor growth in an individual , comprising administering two immunotherapy compositions within a dosing period , the two immunotherapy compositions comprising:a) a first immunotherapy composition comprising a recombinant Ad5 adenovirus comprising a nucleic acid sequence encoding a CEA peptide; andb) a second immunotherapy composition comprising a CEA peptide and either a whole inactivated yeast or yeast lysate.80. The method of claim 79 , wherein the whole inactivated yeast is a whole claim 79 , heat-killed yeast.81Saccharomyces.. The method of claim 79 , wherein the whole inactivated yeast is from82. The method of claim 79 , wherein the first and second immunotherapy compositions are administered to different sites in the individual.83. The method of claim 79 , wherein the first and second immunotherapy compositions are administered to the same site or to adjacent sites in the individual.84. The method of claim 79 , wherein the CEA is human CEA.85. The method of claim 84 , wherein the human CEA is full-length human CEA.86. The method of claim 79 , wherein the CEA comprises a CAP1-6D epitope.87. The method of claim 79 , further comprising boosting the individual with one or both of the immunotherapy compositions.88. The method of claim 87 , wherein boosting the individual is with both immunotherapy compositions.89. The method of claim 88 , further comprising boosting the individual with a third immunotherapy composition comprising a recombinant virus comprising the virus genome or portions thereof that is different from the first immunotherapy composition.90. The method of claim 79 , wherein the individual is ...

ANTI-GLYCO-MUC1 ANTIBODIES AND THEIR USES

The present disclosure relates to anti-glyco-MUC1 antibodies and antigen binding fragments thereof that specifically bind to a cancer-specific glycosylation variant of MUC1 and related fusion proteins and antibody-drug conjugates, as well as nucleic acids encoding such biomolecules. The present disclosure further relates to use of the antibodies, antigen-binding fragments, fusion proteins, antibody-drug conjugates and nucleic acids for cancer therapy. 177-. (canceled)78. A method of treating cancer comprising administering to a subject in need thereof an effective amount of an anti-glyco-MUC1 antibody or antigen binding fragment that:a. comprises a complementarity determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:33, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:29, a CDR-H3 comprising the amino acid sequence of SEQ ID NO:25, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 8, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:9, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:31; and{'sub': '3', '#text': 'b. binds to the MUC1 tandem repeat (VTSAPDTRPAPGSTAPPAHG)(SEQ ID NO:47) that has been glycosylated in vitro using purified recombinant human glycosyltransferases GalNAc-T1, GalNAc-T2, and GalNAc-T4 (referred to hereinafter as the “first epitope”).'}79. A method of treating cancer comprising administering to a subject in need thereof an effective amount of an anti-glyco-MUC1 antibody or antigen binding fragment that:a. comprises a complementarity determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:33, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:29, a CDR-H3 comprising the amino acid sequence of SEQ ID NO:25, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 8, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:9, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:31; andb. preferentially binds to a glyco-MUC1 epitope that is overexpressed on ...

COMPOSITION AND THERAPEUTIC ANTI-TUMOUR VACCINE

The invention relates to a composition which induces, in a host, a cytotoxic cell response directed against cells expressing an antigen, in particular tumour cells, and which comprises red blood cells containing said antigen. These red blood cells may be in the form of an immune complex with an immunoglobulin, in particular IgG, which recognizes an epitope at the surface of the red blood cells, and/or be heat-treated or chemically treated so as to promote phagocytosis of said red blood cells by dendritic cells. As a variant, the red blood cells may be xenogenic red blood cells. The invention also relates to a therapeutic especially anti-tumour vaccine containing such a composition. 137-. (canceled)38. A method for inducing an immune response against a tumour comprising administering to a patient in need thereof an effective amount of a composition comprising red blood cells containing a tumour antigen intracellularly.39. The method of claim 38 , wherein the immune response is a cytotoxic cellular response against tumour cells or a tumour.40. The method of claim 38 , wherein the composition is a vaccine composition.41. The method of claim 38 , wherein the composition further comprises an adjuvant.42. The method of claim 38 , wherein the red blood cells are in the form of an immune complex with an immunoglobulin which recognizes an epitope at the surface of the red blood cells claim 38 , wherein the immune complex promotes phagocytosis of the red blood cells by antigen presenting cells (APCs).43. The method of claim 42 , wherein the red blood cells form an immune complex with an anti-rhesus or anti-glycophorin A or anti-CR1 antibody.44. The method of claim 42 , wherein the immunoglobulin is an IgG.45. The method of claim 38 , wherein the red blood cells are heat-treated or chemically-treated claim 38 , wherein the heat- or chemical-treatment promotes phagocytosis of the red blood cells by APCs.46. The method of claim 42 , wherein the red blood cells in the form of an ...

Compositions and methods of treating renal cell cancer

The present invention provides compositions and methods for treating renal cell carcinoma

Fusion Comprising A Cell Penetrating Peptide, A Multi Epitope And A TLR Peptide Agonist For Treatment Of Cancer

The present invention provides a complex for use in the prevention and/or treatment of cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of cancer, such as a pharmaceutical compositions and vaccines are provided. 1. A method for treating colorectal cancer in a subject in need thereof , the method comprising administering to the subject a complex comprising:a) a cell penetrating peptide;b) at least three antigenic epitopes; andc) at least one TLR peptide agonist,wherein the components a)-c) are covalently linked,wherein the at least three antigenic epitopes comprise (i) one or more epitopes of survivin or (a) functional sequence variant(s) thereof, (ii) one or more epitopes of CEA or (a) functional sequence variant(s) thereof, and (iii) one or more epitopes of ASCL2 or (a) functional sequence variant(s) thereof.2. (canceled)3. The method of claim 1 , wherein the cell penetrating peptide(i) has a length of the amino acid sequence of said peptide of 5 to 50 amino acids in total, and/or(ii) has an amino acid sequence comprising a fragment of the minimal domain of ZEBRA, said minimal domain extending from residue 170 to residue 220 of the ZEBRA amino acid sequence according to SEQ ID NO: 3, wherein, optionally, 1, 2, 3, 4, or 5 amino acids have been substituted, deleted, and/or added without abrogating said peptide's cell penetrating ability, or a variant thereof.46.-. (canceled)7. The method of claim 1 , wherein the cell penetrating peptide has an amino acid sequence comprising or consisting of an amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13) claim 1 , SEQ ID NO: 7 (CPP4/Z14) claim 1 , SEQ ID NO: 8 (CPP5/Z15) claim 1 , or SEQ ID NO: 11 (CPP8/Z18) claim 1 , or sequence variants thereof sharing at least 70% sequence identity without abrogating ...

A MONOPHOSPHORYL LIPID-A LIPOSOME BASED CANCER VACCINE

A vaccine composition for enhancing in a subject to whom the composition is administered, a production of antibodies against a disialoganglioside GD3 and/or GD2 is provided in one embodiment. The composition includes, in an embodiment, a liposome including an effective amount of disialoganglioside GD3 and/or GD2 to stimulate or enhance antibody production in the subject; and an effective amount of an adjuvant comprising monophosphory 1 lipid A (MPL). In one example, the vaccine composition may be administered to the subject in conjunction with a chemotherapy.

CHIMERIC ANTIGEN RECEPTOR COMPRISING INTERLEUKIN-15 INTRACELLULAR DOMAIN AND USES THEREOF

Provided herein are chimeric antigen receptors (CARs) comprising an antigen binding domain (e.g., CD19, CD30, GD2, etc.), transmembrane domain (e.g., CD28), and a cytoplasmic domain (e.g., CD27, 4-1BB, etc.). In some aspects, the disclosure relates to use of the CARs in T cells, compositions, kits and methods.

Immunity-inducing agent

This application provides an immunity-inducing agent comprising, as an active ingredient, at least one polypeptide having immunity-inducing activity and selected from (a) polypeptides consisting of amino acid sequences represented by SEQ ID NO: 8, 4, 6, 10, 12, 2 and 14, and polypeptides consisting of 7 or more consecutive amino acids in the amino acid sequences, (b) polypeptides having a sequence identity of 85% or more with the amino acid sequences represented by SEQ ID NO: 8, 4, 6, 10, 12, 2 and 14, and polypeptides consisting of 7 or more consecutive amino acids in the amino acid sequences, and (c) polypeptides comprising the polypeptides according to (a) or (b) as the partial sequences, or a recombinant vector comprising a polynucleotide encoding the polypeptide and capable of expressing the polypeptide in vivo.

Compositions and methods comprising engineered chimeric antigen receptor and modulator of car

There is provided method for making a cell composition which comprises step of transducing a population of cells with a mixture of at least two viral vectors, wherein at least one vector comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR); and wherein at least one vector comprises a nucleic acid encoding an activity modulator which modulates the activity of the CAR, of a cell expressing the CAR, or of a target cell. There is also provided a cell composition made by such a method and its use in the treatment of diseases such as cancer.

METHOD OF INDIRECT IMMUNIZATION OF HUMAN OVARIAN CANCER PATIENTS THROUGH SELECTION OF XENOGENEIC IMMUNOGLOBULIN FC PORTIONS

The present document describes a method for therapeutic indirect immunization of an optimally debulked human ovarian cancer patient having a CA125 antigen level in the blood above normal levels, comprising administering to said human patient a monoclonal antibody specific to CA125 antigen having at least a xenogeneic Fc region; an immune complex formed between CA125 antigen and said monoclonal antibody having at least a xenogeneic Fc region; or a combination thereof. 1. A method for therapeutic indirect immunization of an optimally debulked human ovarian cancer patient having a CA125 antigen level in the blood above normal levels , comprising administering to the human patient:(a) a monoclonal antibody specific to CA125 antigen having at least a xenogeneic Fc region;(b) an immune complex formed between CA125 antigen and the monoclonal antibody having at least a xenogeneic Fc region; or(c) a combination thereof.2. The method of claim 1 , wherein the CA125 antigen level in the blood above normal levels is more than 35 units/mL of CA125 antigen in the blood.3. The method of claim 1 , wherein the CA125 antigen level in the blood above normal levels is at least 50 units/mL of CA125 antigen in the blood.4. The method of claim 1 , wherein the xenogeneic Fc region is from an IgA claim 1 , IgD claim 1 , IgG claim 1 , or IgM isotype.5. The method of claim 1 , wherein the xenogeneic Fc region is from an IgG isotype.6. The method of claim 5 , wherein the IgG isotype is an IgG1 isotype.7. The method of claim 1 , wherein the xenogeneic Fc region is a murine Fc region claim 1 , a rat Fc region claim 1 , a rabbit Fc region claim 1 , a goat Fc region claim 1 , or a hamster Fc region.810-. (canceled)11. The method of claim 1 , wherein the antibody specific to CA125 is mAb-B43.13 (oregovomab).12. The method of claim 1 , wherein administering is one claim 1 , two claim 1 , three claim 1 , or a maximum of four administrations.13. The method of claim 1 , further comprising administration ...

CELLULAR IMMUNITY INDUCING VACCINE

A novel vaccine that can induce sufficiently high cell-mediated immunity is disclosed. The vaccine of the present invention contains, as an effective component, a polypeptide comprising a tandem repeat structure in which an MHC class I epitope region derived from an antigen protein and a spacer sequence are linked to each other alternately and repeatedly at least three times, or a recombinant vector which comprises a polynucleotide encoding said polypeptide and is capable of expressing said polypeptide in vivo. The spacer sequence is, for example, a sequence generated as an amino acid sequence inevitably encoded by a single base sequence which is designed such that the MHC class I epitope region derived from the antigen protein, an MHC class II epitope region derived from the antigen protein, and at least one higher-order-structure-stabilizing region are encoded by different reading frames in said single base sequence. 1. A method of manufacturing a vaccine , said method comprising:a designing step of designing a multifunctional base sequence in which an MHC class I epitope region, an MHC class II epitope region and at least one higher-order-structure-stabilizing region are encoded separately by three reading frames, wherein the MHC class I epitope region and the MHC class II epitope region are derived from the same antigen protein or different antigen proteins;a production step of producing a polypeptide comprising a tandem repeat structure in which the MHC class I epitope region and a spacer sequence are linked to each other alternately and repeatedly at least three times, or a polynucleotide encoding said polypeptide and is capable of expressing said polypeptide in vivo, wherein said spacer sequence is an amino acid sequence that is generated adjacent to the MHC class I epitope region in a reading reading frame encoding the MHC class I epitope region in the multifunctional base sequence, or an amino acid sequence which is the same amino acid sequence as (1) ...

Cellular immunity inducing vaccine

A novel vaccine that can induce sufficiently high cell-mediated immunity is disclosed. The vaccine of the present invention contains, as an effective component, a polypeptide comprising a tandem repeat structure in which an MHC class I epitope region derived from an antigen protein and a spacer sequence are linked to each other alternately and repeatedly at least three times, or a recombinant vector which comprises a polynucleotide encoding said polypeptide and is capable of expressing said polypeptide in vivo. The spacer sequence is, for example, a sequence generated as an amino acid sequence inevitably encoded by a single base sequence which is designed such that the MHC class I epitope region derived from the antigen protein, an MHC class II epitope region derived from the antigen protein, and at least one higher-order-structure-stabilizing region are encoded by different reading frames in said single base sequence.

CANCER VACCINES AGAINST MUCOSAL ANTIGENS AND METHODS OF MAKING AND USING THE SAME

Nucleic acid molecules comprising a nucleotide sequence that encodes a chimeric protein are disclosed. The chimeric proteins comprise at least one epitope of a mucosally restricted antigen, at least one CD4+ helper epitope, and, optionally, a secretion sequence. Chimeric proteins that comprise at least one epitope of a mucosally restricted antigen, at least one CD4+ helper epitope and, optionally a secretion sequence are also disclosed. Compositions including pharmaceutical compositions and injectables comprising nucleic acid molecule and proteins are disclosed. Methods of treating individuals diagnosed with cancer of a mucosal tissue and methods of preventing cancer of a mucosal tissue are disclosed. 1. A DNA molecule comprising a viral genome in an infectious , recombinant adenovirus vector and further comprises a nucleotide sequence that encodes a chimeric protein , wherein;said chimeric protein comprises guanylyl cyclase C's extracellular domain linked to one universal CD4+ helper epitope PADRE.2. (canceled)3. The DNA molecule of wherein the nucleotide sequence that encodes said chimeric protein further comprises an nucleotide sequence that encodes a secretion sequence.416-. (canceled)17. A composition comprising the DNA molecule of and a carrier or diluent.18. A pharmaceutical composition comprising DNA molecule of and a pharmaceutically acceptable carrier or diluent.19. An injectable pharmaceutical composition comprising the DNA molecule of and a pharmaceutically acceptable carrier or diluent claim 1 , wherein the injectable pharmaceutical composition is sterile and pyrogen free.2031-. (canceled)32. A method of treating an individual who has been diagnosed with cancer having cancer cells that express guanylyl cyclase C claim 18 , comprising the step of administering to the individual an effective amount of a pharmaceutical compound of .3334-. (canceled)35. The method of comprising the step of biopsying a sample of cancer tissue to confirm the presence of ...

Pap peptide analogues

The application provides a polypeptide comprising the sequence SLMTNLAAL, Ser 13 to Leu 21 of amino acid sequence shown in FIG. 1 or SEQ ID No 1, and having HLA-A2 haplotype binding activity, or a polynucleotide encoding said polypeptide. Vaccines containing the polypeptide or polynucleotides encoding the polypeptide are also provided.

Antibodies against immunogenic glycopeptides, compositions comprising the same and use thereof

Disclosed herein are antibodies which specifically bind to at least one epitope defined by the immunogenic glycopeptide. Other aspects of the present disclosure are pharmaceutical composition comprising the antibody; and method for preventing and/or treating Globo-H-positive cancer.

Chimeric antigen receptors (car) and methods for making and using the same

Chimeric antigen receptors (CARs) and CAR-expressing T cells are provided that can specifically target cells that express an elevated level of a target antigen. Likewise, methods for specifically targeting cells that express elevated levels of antigen (e.g., cancer cells) with CAR T-cell therapies are provided.

MEDICINE FOR TREATING CANCER BY ADMINISTERING A TOLL-LIKE RECEPTOR AGONIST AND LAG-3 IgG FUSION PROTEIN

The present invention provides a medicine comprising a Toll-like receptor agonist, LAG-3 protein, a variant or derivative thereof. 1. A medicine for treating a cancer in a patient , comprisinga Toll-like receptor agonist,lymphocyte activation gene 3 (LAG-3) protein or a fusion protein of an extracellular domain of LAG-3 protein and IgG, andan HSP70-derived peptide consisting of SEQ ID NO: 7 and a GPC3-derived peptide consisting of SEQ ID NO: 16.2. The medicine according to claim 1 , for combined administration ofthe Toll-like receptor agonist andLAG-3 protein or a fusion protein of the extracellular domain of LAG-3 protein and IgG, andan HSP70-derived peptide consisting of SEQ ID NO: 7 and a GPC3-derived peptide consisting of SEQ ID NO: 16.3. The medicine according to claim 1 , for use in a cancer vaccine therapy.4. The medicine according to claim 1 , wherein the Toll-like receptor agonist is a Toll-like receptor 3 agonist or a Toll-like receptor 9 agonist.5. The medicine according to claim 1 , wherein the Toll-like receptor agonist is Poly I:C or a salt thereof.6. The medicine according to claim 5 , wherein the Poly I: C is Poly ICLC.7. A medicine for inducing an immune response to a cancer cell in a patient claim 5 , comprisinga Toll-like receptor agonist,lymphocyte activation gene 3 (LAG-3) protein or a fusion protein of an extracellular domain of LAG-3 protein and IgG, andan HSP70-derived peptide consisting of SEQ ID NO: 7 and a GPC3-derived peptide consisting of SEQ ID NO: 16. This application is a Divisional of U.S. application Ser. No. 16/341,415, which is the U.S. National Stage application of PCT/JP2017/015227, filed Apr. 14, 2017, which claims priority from Japanese application no. JP 2016-200227, filed Oct. 11, 2016.The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-WEB and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Feb. 22, 2022, is named sequence.txt and is 6,658 ...

Compositions and methods for generating antigens, antibodies, and immunotherapeutic compositions and methods

In some aspects, the invention relates to compositions and methods of generating antigens, wherein the antigen is a biomolecule that is modified by a reactive oxygen species or a reactive nitrogen species. In some aspects, the invention relates to compositions and methods of generating antibodies that bind to biomolecules that have been modified by a reactive oxygen species or a reactive nitrogen species. In some aspects, the invention relates to compositions and methods of generating antibodies that bind to novel epitopes on unmodified biomolecules. In some aspects, the invention relates to the induction of active immunotherapeutic processes (e.g., using preventive or therapeutic vaccines), which may comprise administering neo-antigens generated through methods and compositions described herein.

DERIVATIVES OF GYLCERO-MANNO-HEPTOSE ADP FOR USE IN MODULATING IMMUNE RESPONSE

The disclosure provides compounds, compositions and methods related to activating alpha-kinase 1 (ALPK1) for modulating an immune response and treating or preventing cancer, infection, inflammation and related diseases and disorders as well as potentiating an immune response to a target antigen. The disclosure also provides heterocyclic compounds of formula (I) as agonists of alpha protein kinase 1 (ALPK1) and their use in activating ALPK1, modulating an immune response and treating diseases such as cancer, wherein A, A, L, L, L, Z, Z, W, W, R, R, R, R, R, Rand Rare as defined herein. 3. The compound according to claim 2 , wherein{'sup': 1', '2, 'Yand Yare independently selected from H, D, —OH, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkanoyloxy and C1-C4 alkenyloxy;'}{'sup': 1', '7', '1', '3', '1', '2', '1', '2, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R-R, L-L, Z, Z, Wand Ware defined as in .'}4. The compound according to claim 2 , wherein{'sup': 1', '2, 'Yand Yare independently selected from —OH, halogen, C1-C4 alkyl and C1-C4 alkanoyloxy;'}{'sup': 1', '7', '1', '3', '1', '2', '1', '2, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R-R, L-L, Z, Z, Wand Ware defined as in .'}6. The compound according to claim 5 , wherein nand nare each 0.7. The compound according to claim 5 , wherein{'sup': 1', '2, 'Xand Xare independently selected from H, D, and C1-C4 alkyl;'}{'sup': 1', '7', '1', '3', '1', '2', '1', '2, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R-R, L-L, Z, Z, Wand Ware defined as in .'}9. The compound according to claim 1 , wherein R claim 1 , R claim 1 , and Rare each H.10. The compound according to claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently selected from the group consisting of —OH claim 1 , and C1-C4 alkanoyloxy.11. The compound according to claim 1 , wherein Lis O.12. The compound according to claim 1 , wherein Lis O.13. The compound according to claim 1 , wherein Lis O or S ...

RNA-NANOSTRUCTURED DOUBLE ROBOTS AND METHODS OF USE THEREOF

Described herein are immuno-stimulatory RNA nanostructures (which comprises a single-stranded RNA (ssRNA) molecule, wherein the ssRNA molecule forms at least one paranemic cohesion crossover), as well as compositions and methods of use thereof. 151.-. (canceled)52. A method of inhibiting tumor growth in a human subject , comprising administering to the subject a therapeutically effective amount of the composition comprising:{'sub': 3', 'n', '1', '2', '4', 'm, 'claim-text': [{'sub': 1', '2, 'NRand NRindependently represent an RNA nanostructure each comprising a nucleic acid sequence having at least about 90% sequence identity to SEQ ID NO:1 or SEQ ID NO: 9 that self-assembles into respective first and second scaffolds;'}, {'sub': 1', '2, 'L is a linker which operably links NRto NR;'}, {'sub': 3', '4, 'wherein Rand Rare independently selected from a pair of fastener strands, an aptamer, a cargo molecule, a capture strand, a targeting strand, and H;'}, 'n is an integer from 1 to 20; and', 'm is an integer from 0 to 20,, 'an RNA nanostructure robot having the sequence of (R)—NR-L-NR—(R), whereinand a pharmaceutically acceptable carrier.53. A method of inducing a tumor necrosis response in a human subject , comprising administering to the subject a therapeutically effective amount of the composition comprising:{'sub': 3', 'n', '1', '2', '4', 'm, 'claim-text': [{'sub': 1', '2, 'NRand NRindependently represent an RNA nanostructure each comprising a nucleic acid sequence having at least about 90% sequence identity to SEQ ID NO:1 or SEQ ID NO: 9 that self-assembles into respective first and second scaffolds;'}, {'sub': 1', '2, 'L is a linker which operably links NRto NR;'}, {'sub': 3', '4, 'Preliminary Amendment dated Jan. 24, 2022 wherein Rand Rare independently selected from a pair of fastener strands, an aptamer, a cargo molecule, a capture strand, a targeting strand, and H;'}, 'n is an integer from 1 to 20; and', 'm is an integer from 0 to 20,, 'an RNA nanostructure ...

NEOEPITOPE VACCINE COMPOSITIONS AND METHODS OF USE THEREOF

In certain embodiments, methods and compositions are provided for generating immune responses against tumor neo-antigens or neo-epitopes. In particular embodiments there may be provided methods for constructing and producing recombinant adenovirus-based vector vaccines containing nucleic acid sequences encoding tumor neo-antigens and neo-epitopes that allow for vaccinations in individuals with preexisting immunity to adenovirus. In additional embodiments, methods and compositions are provided for the treatment of cancer using immunotherapy based on recombinant adenovirus-based vectors combined with engineered natural killer cells. In some embodiments, the methods and compositions further comprises a nucleic acid encoding for an immunological fusion partner. 1153.-. (canceled)154. A method for making a replication-defective adenoviral vector , the method comprising:a. obtaining a tumor sample from a subject;b. identifying tumor specific mutations in the tumor sample comprising whole exome sequencing of the tumor sample;c. identifying expressed mutations from step b by RNA sequencing;d. identifying the neo-antigen from the expressed mutations from step c comprising analyzing the sequences for their predicted binding affinity to MHC Class I molecules, wherein peptide(s) predicted to bind MHC Class I molecules with IC50<500 are neo-antigen(s); ande. packaging a nucleotide encoding the neo-antigen identified in step d into the adenoviral vector,wherein the adenoviral vector further comprises a nucleic acid sequence encoding for an immunological fusion partner having at least 85% sequence identity to any one of SEQ ID NO: 39-SEQ ID NO: 90 or SEQ ID NO: 109-SEQ ID NO: 112.155. The method of claim 154 , wherein the replication-defective adenoviral vector comprises a deletion in an E2B region claim 154 , an E1 region claim 154 , an E3 region claim 154 , and E4 region claim 154 , or any combination thereof.156. The method of claim 154 , wherein the replication-defective ...

IMMUNOSTIMULATORY COMPOSITIONS, PARTICLES, AND USES RELATED THERETO

In some embodiments, described herein is a method of tumor treatment or tumor vaccination. The method generally comprises applying to a human being in need thereof a tumor therapeutic composition or tumor vaccine defined herein. The tumor therapeutic composition or tumor vaccine can be produced by protein transfer of glycosyl-phosphatidylinositol (GPI)-anchored immunostimulatory or costimulatory molecules 1. A method of treating metastatic head and neck squamous cell carcinoma (HNSCC) comprising administering an effective amount of HNSCC cells in combination with an anti-PD-1 antibody to a subject in need thereof , wherein the cells comprise:A B7-1 molecule anchored to a lipid membrane on the exterior of the cells;AndAn IL-12 anchored to the lipid membrane on the exterior of the cells.2. (canceled)3. (canceled)4. The method of claim 1 , wherein the anti-PD-1 antibody is nivolumab.5. The method of claim 1 , wherein the cells are transfected with a vector comprising a nucleic acid encoding HER-2.6. The method of claim 5 , wherein the nucleic acid comprises SEQ ID NO:7.7. The method of claim 1 , wherein one or more of the B7-1 and IL-12 is anchored to the lipid membrane through a conjugated glycosyl-phosphatidylinositol.8. The method of claim 1 , wherein both the B7-1 and IL-12 are anchored to the lipid membrane through a conjugated glycosyl-phosphatidylinositol. This application is a continuation of U.S. application Ser. No. 14/374,729 filed Jul. 25, 2014, which is the National Stage of International Application No. PCT/US2013/024355 filed Feb. 1, 2013, which claims the benefit of U.S. Provisional Application No. 61/594,754 filed Feb. 3, 2012. The entirety of each of these applications is hereby incorporated by reference for all purposes.This invention was made with government support under Grant RO1CA138993 awarded by the National Institutes of Health. The government has certain rights in the invention.The Sequence Listing associated with this application is provided ...

Therapeutic constructs for treating cancer

The present disclosure provides nucleic acid constructs for the treatment of cancer, comprising a cancer-specific promoter and one or more therapeutic genes.

PHARMACEUTICAL COMPOSITION CONTAINING A STABILISED mRNA OPTIMISED FOR TRANSLATION IN ITS CODING REGIONS

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

COMPOSITIONS AND METHODS FOR TUMOR VACCINATION USING PROSTATE CANCER-ASSOCIATED ANTIGENS

Methods and compositions for constructing and producing recombinant adenovirus-based vector vaccines are provided. In particular aspects, there are be provided compositions and methods involving adenovirus vectors comprising genes for target antigens, such as pro state-specific antigen (PSA), pro state-specific membrane antigen (PSMA), MUC1, CEA, and/or Brachyury, and costimulatory molecules for use in treatment methods that generate highly reactive anti-tumor immune responses and that allows for multiple vaccinations in individuals with preexisting immunity to adenovirus. 1. A composition comprising a replication-defective virus vector comprising a nucleic acid sequence encoding a prostate specific antigen (PSA) and/or a nucleic acid sequence encoding prostate-specific membrane antigen (PSMA) , wherein the PSA has an amino acid sequence at least 80% , at least 85% , at least 90% , at least 92% , at least 95% , at least 97% , or at least 99% identical with SEQ ID NO: 1 or SEQ ID NO: 34 or the PSMA has an amino acid sequence at least 80% identical with SEQ ID NO: 11.2. The composition of claim 1 , wherein the vector comprises a nucleic acid sequence encoding a PSA having an amino acid sequence at least 80% claim 1 , at least 85% claim 1 , at least 90% claim 1 , at least 92% claim 1 , at least 95% claim 1 , at least 97% claim 1 , or at least 99% identical with SEQ ID NO: 35 or the nucleic acid sequence encoding PSA has at least 80% claim 1 , at least 85% claim 1 , at least 90% claim 1 , at least 92% claim 1 , at least 95% claim 1 , at least 97% claim 1 , or at least 99% identical with SEQ ID NO: 2.3. The composition of claim 1 , wherein the vector comprises a nucleic acid sequence encoding a PSMA having an amino acid sequence at least 80% claim 1 , at least 85% claim 1 , at least 90% claim 1 , at least 92% claim 1 , at least 95% claim 1 , at least 97% claim 1 , or at least 99% identical with SEQ ID NO: 36.4. The composition of claim 1 , further comprising a second ...

T cell receptors and methods of use thereof

The present disclosure is directed recombinant T cell receptors capable of binding a MUC5AC epitope and nucleic acid molecules encoding the same. In some aspects, the nucleic acid molecules further comprise a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR. Other aspects of the disclosure are directed to vectors comprising the nucleic acid molecule and cells comprising the recombinant TCR, the nucleic acid molecule, or the vector. Still other aspects of the disclosure are directed to methods of using the same. In some aspects, the methods comprise treating a cancer in a subject in need thereof.

PHARMACEUTICAL COMPOSITION CONTAINING A STABILISED mRNA OPTIMISED FOR TRANSLATION IN ITS CODING REGIONS

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

GP96-BASED CANCER THERAPY

The present disclosure relates, inter alia, to compositions and methods for treating cancer, including lung cancer (e.g., Non-Small Cell Lung Cancer), comprising administering (a) a cell harboring an expression vector comprising a nucleotide sequence that encodes a secretable vaccine protein and (b) an immune checkpoint inhibitor to a subject in need thereof. 1. A method of treating lung cancer , comprising administering (a) a cell harboring an expression vector comprising a nucleotide sequence that encodes a secretable vaccine protein and (b) an immune checkpoint inhibitor to a subject in need thereof.2. The method of claim 1 , wherein the immune checkpoint inhibitor inhibits an immune checkpoint gene.3. The method of or claim 1 , wherein the immune checkpoint inhibitor comprises an antibody or antigen binding fragment thereof.4. The method of claim 2 , wherein the immune checkpoint gene is selected from Programmed cell death protein 1 (PD-1) claim 2 , Programmed death-ligand 1 (PD-L1) claim 2 , Programmed death-ligand 1 (PD-L2) claim 2 , Tumor necrosis factor receptor superfamily claim 2 , member 4 (TNFRSF4) claim 2 , tumor necrosis factor receptor superfamily member 25 (TNFRSF25) claim 2 , Death receptor 3 (DR3) claim 2 , Tumor necrosis factor receptor superfamily member 9 (TNFRSF9) claim 2 , Glucocorticoid-induced TNFR-related protein (GITR) claim 2 , Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Lymphocyte-activation gene 3 (LAG-3).5. The method of claim 2 , wherein the immune checkpoint gene is PD-1 or PD-L1.6. The method of any one of - claim 2 , wherein the immune check point inhibitor is an anti-PD-1 or anti-PD-L1 antibody or antigen binding fragment thereof.7. The method of claim 6 , wherein the anti-PD-1 antibody or antigen binding fragment thereof is selected from nivolumab claim 6 , pembrolizumab claim 6 , pidilizumab claim 6 , BMS-936559 claim 6 , atezolizumab claim 6 , avelumab claim 6 , and the PD-L1 antibody or antigen binding fragment ...

Epitopes

The present invention relates to epitopes containing homocitrulline (Hcit) that can be used as targets for cancer immunotherapy. The homocitrullinated T cell epitope has (i) a predicted binding score to MHC class II or class I of <30 using the online IEDB prediction program (http://www.iedb.org/) and (ii) at least 5 consecutive amino acids that form a spiral conformational structure. These modified peptides can be used as vaccines or as targets for T cell receptor (TCR) and adoptive T cell transfer therapies.

Immunity-inducing agent

This application provides an immunity-inducing agent comprising, as an active ingredient, at least one polypeptide having immunity-inducing activity and selected from (a) polypeptides consisting of amino acid sequences represented by SEQ ID NO: 8, 4, 6, 10, 12, 2 and 14, and polypeptides consisting of 7 or more consecutive amino acids in the amino acid sequences, (b) polypeptides having a sequence identity of 85% or more with the amino acid sequences represented by SEQ ID NO: 8, 4, 6, 10, 12, 2 and 14, and polypeptides consisting of 7 or more consecutive amino acids in the amino acid sequences, and (c) polypeptides comprising the polypeptides according to (a) or (b) as the partial sequences, or a recombinant vector comprising a polynucleotide encoding the polypeptide and capable of expressing the polypeptide in vivo.

Methods and Compositions for Dectin-2 Stimulation and Cancer Immunotherapy

Provided are methods and compositions for treating an individual with cancer or infectious disease. Multivalent Dectin-2 stimulating agents are provided that include: (a) an agent that binds to Dectin-2 and stimulates Dectin-2 signaling; and (b) an antibody and/or an immunomodulatory agent, wherein (a) and (b) are conjugated to one another. In some cases, (a) is a mannobiose glycopolypeptide that binds to Dectin-2. In some cases (b) is a stimulatory ligand for a TLR (e.g., TLR7, TLR8, TLR7/8, TLR2, and the like). Methods of treating an individual with cancer and/or an infectious disease can include administering to the individual an effective amount of a Dectin-2 stimulating composition. In some cases, the Dectin-2 stimulating composition comprises a Dectin-2 stimulating glycopolymer. In some cases the Dectin-2 stimulating composition comprises a multivalent Dectin-2 stimulating agent. 1. A multivalent Dectin-2 stimulating agent , comprising:(a) an agent that binds to Dectin-2 and stimulates Dectin-2 signaling; and(b) an antibody and/or an immunomodulatory agent,wherein (a) and (b) are conjugated to one another.2. The multivalent Dectin-2 stimulating agent of claim 1 , wherein (a) is an anti-Dectin-2 antibody or an antigen-binding region thereof.3. The multivalent Dectin-2 stimulating agent of claim 1 , wherein (a) is a mannobiose glycopolypeptide that binds to Dectin-2.4. The multivalent Dectin-2 stimulating agent of claim 3 , wherein the mannobiose glycopolypeptide includes a peptide that is from 20 to 250 amino acids long.5. The multivalent Dectin-2 stimulating agent of claim 4 , wherein said peptide is a mucin-like peptide.6. The multivalent Dectin-2 stimulating agent of claim 3 , wherein the mannobiose glycopolypeptide has a glycan density of at least 25%.7. The multivalent Dectin-2 stimulating agent of claim 1 , wherein (b) is an immunomodulatory agent.8. The multivalent Dectin-2 stimulating agent of claim 1 , wherein (b) is a cytokine selected from: IL-1 ...

Cancer vaccines and vaccination methods

Compositions of multipeptide vaccines comprising at least seven tumor associated antigens, compositions of antigen presenting cell (e.g., dendritic cell) based vaccines presenting epitopes from at least seven tumor associated antigens, and methods of making same, are provided herein. Also, disclosed are methods for treating gynecological and peritoneal cancers using such vaccines.

PHARMACEUTICAL COMPOSITIONS COMPRISING ONCOLYTIC HERPES SIMPLEX VIRUS FOR SYSTEMIC ADMINISTRATION

Disclosed is a pharmaceutical composition comprising oncolytic herpes simplex virus expressing IL12 and PD-1 antibody for treatment of cancer through systemic administration. 1. A pharmaceutical composition for treatment of cancer in a subject , comprising a therapeutically effective amount of an oncolytic herpes simplex virus (oHSV) , wherein the oHSV is modified compared to wild type herpes simplex virus to have (i) a deletion between the promoter of U56 gene and the promoter of Us1 gene , and (ii) an addition of a heterologous nucleic acid sequence encoding an immunostimulatory agent and/or an immunotherapeutic agent , and wherein the pharmaceutical composition is formulated for systemic delivery to the subject.2. The pharmaceutical composition of claim 1 , wherein the immunostimulatory agent is selected from a group consisting of GM-CSF claim 1 , IL 2 claim 1 , IL 5 claim 1 , IL 12 claim 1 , IL 15 claim 1 , IL 24 and IL 27.3. The pharmaceutical composition of claim 1 , wherein the immunotherapeutic agent is selected from a group consisting of an anti-PD-1 agent and an anti-CTLA-4 agent.4. The pharmaceutical composition of claim 1 , wherein the oHSV expresses both an immunostimulatory agent and an immunotherapeutic agent.5. The pharmaceutical composition of claim 1 , wherein the oHSV expresses IL-12 and an anti-PD-1 antibody.6. The pharmaceutical composition of claim 1 , wherein the oHSV is originated from herpes simplex virus serotype 1 (HSV-1).7. The pharmaceutical composition of claim 6 , wherein the HSV-1 is selected from strains F claim 6 , KOS claim 6 , and 17.8. The pharmaceutical composition of claim 7 , wherein the HSV-1 is F strain of HSV-1.9. The pharmaceutical composition of claim 1 , wherein the oHSV contains a deletion of nucleotide positions 117005 to 132096 in the genome of F strain of HSV-1.10. The pharmaceutical composition of claim 1 , wherein the oHSV is not encapsulated within or conjugated by a carrier.11. The pharmaceutical composition of ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST PANCREATIC CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, 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 tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of treating cancer in a HLA-A*02+ patient , wherein said cancer comprises cancer cells that overexpress a COL6A3 polypeptide and present at their surface in complex with an MHC class I molecule a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 9 , 1-8 , 12-20 , 22-36 , 38-64 , and 66-87 , said method comprising administering to said patient an effective amount of activated antigen-specific CD8+ cytotoxic T cells to kill cancer cells , wherein said activated antigen-specific CD8+ cytotoxic T cells are produced by contacting in vitro CD8+ cytotoxic T cells with an antigen presenting cell presenting at its surface in complex with an MHC class I molecule a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 9 , 1-8 , 12-20 , 22-36 , 38-64 , and 66-87 , wherein said cancer is selected from pancreatic cancer , colon or rectal cancer , melanoma , esophageal cancer , ovarian cancer , breast cancer , small cell lung cancer , urinary bladder cancer , gall bladder cancer , and bile duct cancer.2. The method of claim 1 , wherein the cytotoxic T cells produced by contacting CD8+ cytotoxic T cells with said antigen presenting cell are cytotoxic T cells autologous to the ...

COMPOSITIONS AND METHODS FOR TUMOR VACCINATION AND IMMUNOTHERAPY INVOLVING HER ANTIGENS

In certain embodiments, methods and compositions are provided for generating immune responses against tumor antigens such as antigens or epitopes of HER1, HER2/neu, HER3, HER4, or any combination thereof. In particular embodiments, there may be provided methods for constructing and producing recombinant adenovirus-based vector vaccines containing nucleic acid sequences encoding tumor antigens such as antigens or epitopes of HER1, HER2/neu, HER3, HER4, or any combination thereof, that allow for vaccinations in individuals with preexisting immunity to adenovirus. 1. A composition comprising:a recombinant adenovirus vector comprising a nucleic acid sequence encoding a full length HER3 antigen or a nucleic acid sequence encoding a truncated HER3 antigen;a recombinant adenovirus vector comprising a nucleic acid sequence encoding a MUC1 antigen; anda recombinant adenovirus vector comprising a nucleic acid sequence encoding a Brachyury antigen.2. A composition comprising a recombinant adenovirus vector comprising:a deletion in an E2b region of the recombinant adenovirus vector; anda nucleic acid sequence encoding a truncated HER3 antigen comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% sequence identity to SEQ ID NO: 6 or SEQ ID NO: 87.3. A composition comprising:a recombinant adenovirus vector comprising a nucleic acid sequence encoding a full length HER3 antigen or a nucleic acid sequence encoding a truncated HER3 antigen; anda recombinant adenovirus vector comprising a nucleic acid sequence encoding a costimulatory molecule.415.-. (canceled)16. The composition of claim 1 , further comprising a nucleic acid sequence encoding an immune checkpoint inhibitor claim 1 , an immune checkpoint modulator claim 1 , combination thereof claim 1 , or an antibody that activates or potentiates an immune response.17. (canceled)18. The composition of claim 1 , further comprising a recombinant adenovirus vector comprising a nucleic acid ...

Fusion Comprising A Cell Penetrating Peptide, A Multi Epitope And A TLR Peptide Agonist For Treatment Of Cancer

The present invention provides a complex for use in the prevention and/or treatment of cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of cancer, such as a pharmaceutical compositions and vaccines are provided. 1117.-. (canceled)118. A method for eliciting or improving an immune response against one or more antigens selected from survivin , carcino-embryonic antigen (CEA) and achaete-scute homolog 2 (ASCL2) in a subject , wherein the immune response comprises presentation of multiple epitopes of the antigen(s) by MHC class I and/or MHC class II molecules , and wherein the method comprises administering a complex comprising:a) a cell penetrating peptide; (i) a peptide having an amino acid sequence according to SEQ ID NO: 95,', '(ii) a peptide having an amino acid sequence according to SEQ ID NO: 96, and', '(iii) a peptide having an amino acid sequence according to SEQ ID NO: 97; and, 'b) at least three antigenic peptides comprising'}c) at least one TLR peptide agonist,wherein the components a)-c) are covalently linked to the subject.119. The method of claim 118 , wherein the cell penetrating peptide(i) has a length of the amino acid sequence of said peptide of 5 to 50 amino acids in total, and/or(ii) has an amino acid sequence comprising a fragment of the minimal domain of ZEBRA, the minimal domain extending from residue 170 to residue 220 of the ZEBRA amino acid sequence according to SEQ ID NO: 3, wherein 0, 1, 2, 3, 4, or 5 amino acids have been substituted, deleted, and/or added without abrogating said peptide's cell penetrating ability.120. The method of claim 118 , wherein the cell penetrating peptide has an amino acid sequence comprising or consisting of an amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13) claim 118 , SEQ ID NO: 7 ( ...

CANCER VACCINE

The present disclosure relates to an immunogenic agent comprising Dna J heat shock protein family (Hsp40) member B7 or an immunogenic fragment thereof; a DNA vaccine comprising a nucleic acid encoding said protein or at least one immunogenic fragment thereof; a pharmaceutical composition or vector or DNA vaccine for use in the treatment of cancer; and a method of treating cancer comprising the use of said immunogenic agent or pharmaceutical composition or vector or DNA vaccine. 1. An immunogenic agent for use as a cancer vaccine comprising or consisting of DnaJ heat shock protein family (Hsp40) member B7 (termed DNAJB7) or at least one immunogenic fragment thereof.2. The immunogenic agent wherein DNAJB7 is human DNAJB7.3. The immunogenic agent according to wherein DNAJB7 is represented by the amino acid sequence set forth in SEQ ID NO: 31 or a sequence having at least 85% claim 2 , 86% claim 2 , 87% claim 2 , 88% claim 2 , 89% claim 2 , 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 therewith.4. The immunogenic agent according to claim 1 , wherein said at least one fragment is 5-30 amino acids in length.7. A vector or DNA vaccine comprising a nucleic acid molecule encoding a DnaJ heat shock protein family (Hsp40) member B7 (termed DNAJB7) claim 1 , or at least one immunogenic fragment thereof claim 1 , according to .8. The vector or DNA vaccine according to wherein said nucleic acid molecule is part of claim 7 , or provided in claim 7 , an expression vector adapted to express said DNAJB7 claim 7 , or at least one of said fragments thereof.9. The vector or DNA vaccine according to wherein said adaptation includes the provision of at least one transcription control sequences which mediate(s) said expression.10. The vector or DNA vaccine according to wherein the at least one transcription control sequence(s) is/are cell/tissue specific and adapted for inducible or constitutive ...

Anti-Tumour Response to Modified Self-Epitopes

Anti-tumour immune responses to modified self-epitopes. The present invention relates to the use of tumour-associated epitopes in medicine and in particular in the treatment of cancer. The epitopes stimulate an immune reaction against the tumour and have a modification selected from determination of arginine to citrulline, nitration of tyrosine, oxidation of tryptophan and deamination of glutamine or asparagine. The invention also relates to nucleic acids comprising sequences that encode such epitopes for use in the treatment of cancer. 1. A tumour-associated epitope which stimulates an immune reaction against the tumour , the epitope having a modification selected from determination of arginine to citrulline , wherein the epitope is derived from cytokeratin 8.3. A method of treating cancer in a patient comprising administering to the patient an effective amount of an epitope of claim 1 , wherein the cancer is melanoma claim 1 , breast claim 1 , endometrial claim 1 , colorectal or ovarian cancer.4. The method of claim 3 , wherein the patient is a human. This application is a divisional of U.S. application Ser. No. 16/007,944, filed Jun. 13, 2018, which is a continuation of U.S. application Ser. No. 14/614,964, filed on Feb. 5, 2015, now U.S. Pat. No. 10,233,220, issued Mar. 19, 2019, which is a continuation of International Application No. PCT/GB2013/052109, which designated the United States and was filed on Aug. 7, 2013, published in English. This application claims priority under 35 U.S.C. § 119 or 365 to Great Britain, Application No. 1214007.5, filed Aug. 7, 2012. The entire teachings of the above applications are incorporated herein by reference.The present invention relates generally to modified peptides that can be used as targets for cancer immunotherapy. These modified peptides can be used as vaccines or as targets for monoclonal antibody (mAb) therapy. Such vaccines or mAbs may be used in the treatment of cancer.The focus of anti-tumour immune responses ...

TREATMENT METHODS

Methods and compositions for identifying tumor antigens of human lymphocytes, and for identifying subjects for cancer therapy, are provided herein. 1282-. (canceled)284. The immunogenic composition of claim 283 , wherein the immunogenic composition does not comprise: (iii) one or more tumor antigens that increase level of expression and/or secretion of one or more immune mediators associated with at least one deleterious and/or non-beneficial response to cancer claim 283 , and/or (iv) one or more tumor antigens that inhibit and/or suppress level of expression and/or secretion of one or more immune mediators associated with at least one beneficial response to cancer claim 283 , or immunogenic fragments thereof.285. The immunogenic composition of claim 283 , wherein the immunogenic composition comprises: (i) one or more antigens that increase a level of expression and/or secretion of one or more immune mediators associated with at least one beneficial response to cancer claim 283 , and/or (ii) one or more tumor antigens that inhibit and/or suppress a level of expression and/or secretion of one or more immune mediators associated with at least one deleterious and/or non-beneficial response to cancer claim 283 , or immunogenic fragments thereof.286. A method of manufacturing an immunogenic composition claim 283 , the method comprising: a) obtaining, providing, or generating a library comprising bacterial cells or beads comprising a plurality of tumor antigens, wherein each bacterial cell or bead of the library comprises a different tumor antigen;', 'b) contacting the bacterial cells or beads with antigen presenting cells (APCs) from a subject, wherein the APCs internalize the bacterial cells or beads;', 'c) contacting the APCs with lymphocytes from the subject, under conditions suitable for activation of lymphocytes by a tumor antigen presented by one or more APCs;', 'd) determining whether one or more lymphocytes are activated by one or more tumor antigens presented by ...

Antibody to Mucin 4 (MUC4) Glycopeptide and Uses Thereof

The present invention provides: an antibody that has specificity for MUC 4 having a sugar chain structure that is expressed at a high level in cancer cells; a glycopeptide that constitutes an antigen that is suitable for producing this antibody; and a new means and method for the diagnosis, prevention, and/or treatment of cancer by means of the aforementioned antibody. The present invention relates to a monoclonal antibody against a glycopeptide. The glycopeptide comprises a human MUC 4 tandem unit peptide having an amino acid sequence represented by SEQ ID NO: 1, and an O-linked sugar chain. The O-linked sugar chain is N-acetylgalactosamine (GalNAc) and binds to threonine, which is the 8th amino acid of the tandem unit peptide. The present invention further includes: a glycopeptide for use in the production of a monoclonal antibody against human MUC 4; a method for detecting MUC 4 in a human body fluid sample; a kit that includes the abovementioned monoclonal antibody; and a pharmaceutical composition for the prevention and/or treatment of malignant tumors that contains the abovementioned monoclonal antibody as an active component.

Combination Therapy for Treating Cancer with a Poxvirus Expressing a Tumor Antigen and an Antagonist of an Immune Checkpoint Inhibitor

The present disclosure encompasses therapies, compositions, and methods for treatment of a human cancer patient using a recombinant poxvirus encoding a tumor-associated antigen in combination with one or more agonists or antagonists of immune checkpoint inhibitors. 2. The method according to claim 1 , wherein (b) further comprises administering to the subject an anti-LAG-3 antagonist that is an antibody.3. The method according to claim 1 , wherein the orthopoxvirus is MVA-BN.4. The method according to claim 1 , further comprising administering to the subject a subsequent administration comprising:(a) a recombinant avipoxvirus comprising a nucleic acid encoding the MUC-1 polypeptide and a nucleic acid encoding the CEA polypeptide; and(b) the anti-PD-1 antagonist that is an antibody.5. The method according to claim 4 , wherein the avipoxvirus is a fowlpoxvirus.6. The method according to claim 1 , wherein said subject has a cancer selected from the group consisting of: breast cancer claim 1 , lung cancer claim 1 , gastric cancer claim 1 , pancreatic cancer claim 1 , bladder cancer claim 1 , and ovarian cancer.7. A method for decreasing tumor burden tumors in a subject-comprising:(a) administering to the subject a priming dose of a recombinant orthopoxvirus comprising a nucleic acid encoding a MUC-1 polypeptide and a nucleic acid encoding a CEA polypeptide in combination with an anti-PD-1 antagonist that is an antibody; and(b) administering to the subject one or more boosting doses of a recombinant avipoxvirus comprising a nucleic acid encoding the MUC-1 polypeptide and a nucleic acid encoding the CEA polypeptide in combination with the anti-PD-1 antagonist that is an antibody.8. The method according to claim 7 , wherein the orthopoxvirus is MVA-BN.9. The method according to claim 7 , wherein the avipoxvirus is a fowlpoxvirus.10. The method according to claim 7 , wherein the cancer treatment is directed against breast cancer claim 7 , lung cancer claim 7 , gastric ...

CANCER VACCINES TARGETING MUC16 AND USES THEREOF

Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a modified consensus MUC16 antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a modified consensus MUC16 antigen are disclosed. Methods of treating a subject with a MUC16-expressing tumor and methods of preventing a MUC16-expressing tumor are disclosed. Modified consensus MUC16 antigen is disclosed. 1. A nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:(a) a nucleic acid sequence that encodes amino acids 19-1490 of SEQ ID NO: 2;(b) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of a protein comprising amino acids 19-1490 of SEQ ID NO: 2;(c) a nucleic acid sequence that encodes a protein that is at least 95% identical to amino acids 19-1490 of SEQ ID NO: 2; and(d) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of a protein that is at least 95% identical to amino acids 19-1490 of SEQ ID NO: 2.2. A nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:(a) nucleotides 55-4470 of SEQ ID NO: 1;(b) a fragment comprising at least 90% an entire length of a nucleic acid molecule comprising nucleotides 55-4470 of SEQ ID NO: 1;(c) a fragment that is at least 95% identical to nucleotides 55-4470 of SEQ ID NO: 1; and(d) a fragment comprising at least 90% of an entire length of a nucleic acid sequence that is at least 95% identical to nucleotides 55-4470 of SEQ ID NO: 1.3. A nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:(a) a nucleic acid sequence that encodes SEQ ID NO: 2;(b) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of SEQ ID NO: 2;(c) a nucleic acid sequence that encodes a protein that is at least 95% identical to SEQ ID NO ...

Methods for enhancing the efficacy of a tumor-directed immune response

As described below, the present invention features methods for enhancing the efficacy of a tumor antigen in inducing an anti-cancer immune response in a subject by administering an OX40 agonist and an Indoleamine 2,3-dioxygenase (IDO) inhibitor with the tumor antigen.

NANT CANCER VACCINE

Cancer is treated using coordinated treatment regimens that uses various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting. 1. A method of treating cancer in a patient in need thereof , the method comprising administering to the patient a sequence of therapeutics , wherein the sequence comprises a platinum chemotherapeutic , Nab-paclitaxel , a means for binding PD-1 , and IL-15 or an IL-15 superagonist.2. The method of claim 1 , wherein the sequence further comprises haNK cells.3. The method of claim 1 , wherein the means for binding PD-1 is nivolumab.4. The method of claim 3 , wherein the IL-15 superagonist is ALT-803.5. The method of claim 4 , wherein the cancer is non-small cell lung cancer.6. The method of claim 5 , wherein the sequence is administered in a 4-week cycle.7. The method of claim 6 , wherein the platinum chemotherapeutic is administered on day 1 of the cycle.8. The method of claim 6 , wherein the Nab-paclitaxel is administered on days 1 claim 6 , 8 claim 6 , and 15 of the cycle.9. The method of claim 6 , wherein the nivolumab is administered on day 8 of the cycle.10. The method of claim 7 , wherein the platinum chemotherapeutic claim 7 , the nivolumab claim 7 , and the Nab-paclitaxel are administered intravenously claim 7 , and wherein the ALT-803 is administered subcutaneously.11. The method of claim 2 , wherein the means for binding PD-1 is nivolumab.12. The method of claim 11 , wherein the sequence comprises an IL-15 superagonist.13. The method of claim 12 , wherein the IL-15 superagonist is ALT-803.14. The method of claim 13 , wherein the cancer is non-small cell lung cancer.15. The method of claim 14 , wherein the sequence is administered in a 4-week cycle.16. The method of claim 15 , wherein the platinum chemotherapeutic is administered on day 1 of the cycle.17. The method of claim 15 , wherein the Nab-paclitaxel is administered on days 1 ...

TARGETING THE TUMOR MICROENVIRONMENT USING MANIPULATED NKT CELLS

The present invention regards methods and/or compositions related to Natural Killer T cells that are engineered to harbor an expression construct that encodes IL-2, IL-4, IL-7, and/or IL-15 and additionally or alternatively comprise a chimeric antigen receptor (CAR). In specific embodiments, the CAR is a CAR that targets the GD2 antigen, for example in neuroblastoma. 114.-. (canceled)15. A method for treating a cancer comprising administering a therapeutically effective number of engineered natural killer T-cells comprising an expression construct that encodes IL-2 , IL-4 , IL-7 , IL-15 , or a combination thereof to a subject in need thereof.16. The method of claim 15 , wherein the natural killer T-cell comprises an inducible suicide gene.17. The method of claim 15 , further comprising inducing the elimination of the administered natural killer T-cell by activating the inducible suicide gene.18. The method of claim 17 , wherein the inducible suicide gene is inducible caspase-9 suicide gene.19. The method of claim 18 , further comprising administering AP20187 claim 18 , AP1903 claim 18 , or a mixture thereof to the subject to activate the inducible caspase-9 suicide gene.20. The method of claim 17 , wherein the inducible suicide gene is thymidine kinase (sr39 TK).21. The method of claim 20 , further comprising administering ganciclovir to the subject to activate the thymidine kinase.229. The method of claim claim 20 , wherein the natural killer T-cell comprises a CD34 tag.23. The method of claim 15 , wherein the cancer is a tumor.24. The method of claim 23 , wherein the tumor microenvironment is hypoxic.25. The method of claim 23 , wherein the tumor microenvironment comprises less than 15% O claim 23 , less than 10% O claim 23 , less than 5% O claim 23 , less than 4% O claim 23 , less than 3% O claim 23 , less than 2% O claim 23 , or less than 1% O.26. The method of claim 15 , wherein the cancer is selected from the group consisting of breast cancer claim 15 , ...

Immuno-Oncology Compositions and Methods for Use Thereof

The compositions and methods are described for generating an immune response to a tumor associated antigen such as MUC-1. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to MUC-1 in the subject to which the vector is administered and boosting the immune response by administering a MUC-1 peptide. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat neoplasms and associated diseases. 1. A immunogenic composition comprising:a) a recombinant modified vaccinia ankara (MVA) viral vector comprising a sequence encoding hypoglycosylated MUC-1 or fragment thereof and a matrix protein sequence, andb) a MUC-1 peptide.2. The composition of wherein the MUC-1 peptide comprises an immunogenic intracellular domain fragment of MUC-1 with sequence 407-475 of GenBank Protein Accession Number NP_001191214 or an immunogenic fragment thereof.3. The composition of wherein the MUC-1 peptide comprises an an immunogenic extracellular domain fragment of MUC-1 (for example sequence 20-376 of GenBank Protein Accession Number NP_001191214 or an immunogenic fragment thereof.4. The composition of wherein the MUC-1 peptide comprises a sequence TSAPDTRPAP (SEQ ID NO:1)5. The composition of wherein the MUC-1 peptide comprises a sequence AHGVTSAPDTRPAPGSTAPP (SEQ ID NO:2).6. The composition of wherein the MUC-1 peptide comprises a sequence AHGVTSAPDNRPALGSTAPP (SEQ ID NO:3).7. The composition of wherein the MUC-1 peptide comprises a sequence AHGVTSAPDTRPAPGSTAPPAHGVTSAPDNRPALGSTAPP (SEQ ID NO:4).9. The composition of wherein the MUC-1 peptide comprises a sequence GenBank Protein Accession Number NP_001191214 (SEQ ID NO:6).10. The composition of wherein the MUC-1 peptide comprises a sequence SKKKKGCKLFAVWKITYKDTGTSAPDTRPAP (SEQ ID NO:7)) wherein the threonine at position 27 is ...

BRACHYURY DELETION MUTANTS, NON-YEAST VECTORS ENCODING BRACHYURY DELETION MUTANTS, AND THEIR USE

The invention provides Brachyury deletion mutant polypeptides, nucleic acids encoding the polypeptides, non-yeast vectors comprising the nucleic acids, non-yeast cells, and methods of use. 1. (canceled)2. A nucleic acid encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 3.3. A non-yeast vector comprising the nucleic acid of .4. The vector of claim 3 , wherein the vector is selected from the group consisting of a plasmid claim 3 , poxvirus claim 3 , retrovirus claim 3 , adenovirus claim 3 , herpes virus claim 3 , polio virus claim 3 , alphavirus claim 3 , baculovirus claim 3 , Sindbis virus claim 3 , or a bacterial vector.5ListeriaSalmonella. The vector of claim 4 , wherein the bacterial vector is a or vector.6. The vector of claim 4 , wherein the vector is a poxvirus selected from the group consisting of orthopox claim 4 , avipox claim 4 , capripox claim 4 , and suipox virus.7. The vector of claim 6 , wherein the poxvirus is selected from the group consisting of vaccinia claim 6 , fowlpox claim 6 , and canarypox virus.8. The vector of claim 3 , further comprising a nucleic acid encoding an immunostimulatory/regulatory molecule.9. The vector of claim 8 , wherein the immunostimulatory/regulatory molecule is selected from the group consisting of interleukin (IL)-2 claim 8 , IL-4 claim 8 , IL-6 claim 8 , IL-12 claim 8 , interferon (IFN)-γ claim 8 , tumor necrosis factor (TNF)-α claim 8 , B7.1 claim 8 , B7.2 claim 8 , ICAM-1 claim 8 , LFA-3 claim 8 , CD70 claim 8 , RANTES claim 8 , G-CSF claim 8 , OX-40L claim 8 , 41 BBL claim 8 , anti-CTLA-4 claim 8 , and combinations thereof.10. The vector of claim 3 , further comprising a nucleic acid encoding one or more tumor associated antigens.11. A non-yeast cell comprising (i) a polypeptide comprising the amino acid sequence of SEQ ID NO: 3 claim 2 , (ii) the nucleic acid of claim 2 , or (iii) a non-yeast vector comprising the nucleic acid.12. The cell of claim 10 , wherein the cell is an antigen presenting ...

Novel peptides and combination of peptides for use in immunotherapy against pancreatic cancer and other cancers

The present invention relates to peptides, proteins, 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 tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

DE NOVO BINDING DOMAIN CONTAINING POLYPEPTIDES AND USES THEREOF

Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications. 277-. (canceled) This application is a continuation of U.S. application Ser. No. 16/817,755, filed Mar. 13, 2020, which is a continuation of U.S. application Ser. No. 15/564,325, 371(c) date Oct. 4, 2017, now U.S. Pat. No. 10,662,248, issued May 26, 2020, which is a U.S. National Phase of PCT Application No. PCT/US2016/025868, filed Apr. 4, 2016, which claims priority to U.S. Provisional Application Ser. No. 62/143,772, filed Apr. 6, 2015, the entirety of each of which is incorporated by reference herein. All references, patents and patent applications referred to herein are herein incorporated by reference in their entireties.The present application is being filed accompanied by a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 6666_0063 Sequence_Listing.txt, created Apr. 12, 2021, and which is 147 kilobytes in size. The information in the Sequence Listing is incorporated herein by reference in its entirety.Antibody-based reagents have accelerated the pace of biological research and development. Antibody compositions represent one of the most important and successful classes of therapeutic and diagnostic agents utilized in the pharmaceutical industry. However, cost, time and efficacy have motivated the development of alternative affinity reagents.A variety of non-antibody binding formats have emerged for applications historically served by antibodies. While many successes have been ...

Novel glycan conjugates and methods of use thereof

The present disclosure is directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA3/SSEA4/GloboH associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globo-series glycosphingolipid synthesis. The present disclosure relates to methods and compositions which can modulate the globo-series glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globo-series glycosphingolipid SSEA3/SSEA4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globo-series synthetic pathway. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions.

METHODS OF ENHANCING IMMUNOGENICITY OF POORLY IMMUNOGENIC ANTIGEN-SPECIFIC VACCINES USING ORAL YEAST BETA-GLUCANS

The present disclosure provides methods for enhancing the immunogenicity of a poorly immunogenic antigen-specific vaccine as well as methods for promoting diversification of the gut microbiome in a subject in need thereof comprising administering to the subject an effective amount of a beta-glucan extract derived from yeast. Kits for use in practicing the methods are also provided. 1. A method for enhancing the immunogenicity of a poorly immunogenic antigen-specific vaccine in a subject in need thereof comprising: (i) comprises at least one poorly immunogenic antigen that is optionally linked to a carrier, wherein the at least one poorly immunogenic antigen is a peptide, a polypeptide, a nucleic acid, a carbohydrate, or a lipid; and', '(ii) is not a whole cell tumor vaccine; and, '(a) administering to the subject an effective amount of the poorly immunogenic antigen-specific vaccine, wherein the poorly immunogenic antigen-specific vaccine'}(b) administering to the subject an effective amount of a yeast beta-glucan comprising a plurality of β-(1,3) side chains linked to a β-(1,3) backbone via β-(1,6) linkages, and wherein the yeast beta-glucan has a range of average molecular weights from about 6 kDa to about 30 kDa, andwherein the immunogenicity of the poorly immunogenic antigen-specific vaccine in the subject is increased compared to that observed in a control subject that is not treated with the yeast beta-glucan.2. The method of claim 1 , wherein the subject is an immunocompromised subject claim 1 , a pediatric subject claim 1 , a geriatric subject claim 1 , or a healthy subject.3. The method of claim 1 , wherein the at least one poorly immunogenic antigen is a peptide claim 1 , a polypeptide claim 1 , a nucleic acid claim 1 , a carbohydrate claim 1 , or a lipid that is associated with a disease or infection.4. The method of claim 3 , wherein the disease or infection is selected from the group consisting of neurodegenerative disease claim 3 , Alzheimer's Disease ...

METHOD OF INDIRECT IMMUNIZATION OF HUMAN OVARIAN CANCER PATIENTS THROUGH SELECTION OF XENOGENEIC IMMUNOGLOBULIN FC PORTIONS

The present document describes a method for therapeutic indirect immunization of an optimally debulked human ovarian cancer patient having a CA125 antigen level in the blood above normal levels, comprising administering to said human patient a monoclonal antibody specific to CA125 antigen having at least a xenogeneic Fc region; an immune complex formed between CA125 antigen and said monoclonal antibody having at least a xenogeneic Fc region; or a combination thereof. 1. A method for therapeutic indirect immunization of an optimally debulked human ovarian cancer patient having a CA125 antigen level in the blood above normal levels , comprising administering to the human patient:(a) a monoclonal antibody specific to CA125 antigen having at least a xenogeneic Fc region;(b) an immune complex formed between CA125 antigen and the monoclonal antibody having at least a xenogeneic Fc region; or(c) a combination thereof.2. The method of claim 1 , wherein the CA125 antigen level in the blood above normal levels is more than 35 units/mL of CA125 antigen in the blood.3. The method of claim 1 , wherein the CA125 antigen level in the blood above normal levels is at least 50 units/mL of CA125 antigen in the blood.4. The method of claim 1 , wherein the xenogeneic Fc region is from an IgA claim 1 , IgD claim 1 , IgG claim 1 , or IgM isotype.5. The method of claim 1 , wherein the xenogeneic Fc region is from an IgG isotype.6. The method of claim 5 , wherein the IgG isotype is an IgG1 isotype.7. The method of claim 1 , wherein the xenogeneic Fc region is a murine Fc region claim 1 , a rat Fc region claim 1 , a rabbit Fc region claim 1 , a goat Fc region claim 1 , or a hamster Fc region.810-. (canceled)11. The method of claim 1 , wherein the antibody specific to CA125 is mAb-B43.13 (oregovomab).12. The method of claim 1 , wherein administering is one claim 1 , two claim 1 , three claim 1 , or a maximum of four administrations.13. The method of claim 1 , further comprising administration ...

Vaccine Nanotechnology

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Hla-a24 agonist epitopes of muc1-c oncoprotein and compositions and methods of use

The invention provides a human cytotoxic T lymphocyte (CTL) agonist epitope from the C-terminal subunit of mucin 1 (MUC1-C), which can be used as a peptide, polypeptide (protein), and/or in vaccine or other composition for the prevention or therapy of cancer. The invention further provides a nucleic acid encoding the peptide, protein, or polypeptide, a vector comprising the nucleic acid, a cell comprising the peptide, polypeptide, nucleic acid, or vector, and compositions thereof.

Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy

The success of anti-tumor immune responses requires effector T cells to infiltrate solid tumors, a process guided by chemokines. Herein, we demonstrate that in vivo post-translational processing of chemokines by dipeptidylpeptidase 4 (DPP4, also known as CD26) limits lymphocyte migration to sites of inflammation and tumors. Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10, and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade. These findings provide the first direct in vivo evidence for controlling lymphocyte trafficking through CXCL10 cleavage and support the use of DPP4 inhibitors for stabilizing the biologically active form of chemokines as a strategy to enhance tumor immunotherapy.

SYNTHETIC LIPOPEPTIDE VACCINES AND IMMUNOTHERAPEUTICS

Single molecules useful in vaccine compositions, and methods of making and using the same, are described. 2. The composition of claim 1 , wherein the composition is formulated in liposomes.3. The composition of claim 2 , wherein the liposomes comprise 1 claim 2 ,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) claim 2 , cholesterol claim 2 , and 1 claim 2 ,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (DSPE-PEG-MAL).4. The composition of claim 2 , wherein the liposomes comprise cholesterol-TEG-Rha claim 2 , cholesterol claim 2 , and 1 claim 2 ,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC).5. The composition of claim 2 , wherein the liposomes are conjugated to an antibody.6. The composition of claim 5 , wherein the antibody comprises anti-mouse F4/80.7. The composition of claim 1 , wherein Z is a Calkyl chain.8. The composition of claim 1 , wherein the T-cell epitope is selected from the group consisting of: QYIKANSKFIGITEL (SEQ ID NO: 1); KLFAVWKITYKDTG (SEQ ID NO: 2); YAFKYARHANVGRNAFELFL (SEQ ID NO: 3); ISQAVHAAHAEINEAGR (SEQ ID NO: 4); and A′KZVAAWTLKAA′ (SEQ ID NO: 5) claim 1 , wherein A′ is D-alanine claim 1 , and Z is L-cyclohexylalanine.11. The composition of claim 1 , wherein Rcomprises a pathogenic or altered diabetic peptide sequence selected from the group consisting of: GTTMVSYQPLGDKV (SEQ ID NO: 6) claim 1 , SYQPLGDKV (SEQ ID NO: 7) claim 1 , SYQPLGDAV (SEQ ID NO: 8) claim 1 , GTTMVSYQPLGDAV (SEQ ID NO: 9) claim 1 , SYQPLGDKA (SEQ ID NO: 10) claim 1 , and GTTMVSYQPLGDKA (SEQ ID NO: 11).12. The composition of claim 1 , wherein Rcomprises a xenoantigen attached to either serine (S) or threonine (T).14. The composition of claim 1 , wherein Rcomprises a cluster of two or more Rhamnose epitopes.15. The composition of claim 1 , wherein Rcomprises a cluster of three Rhamnose epitopes.23. The composition of claim 22 , wherein the protected PamCysSK-DBCO conjugate (7) (“CysSK” disclosed as SEQ ID NO: 16) comprises a t- ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST PANCREATIC CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, 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 tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of treating cancer in a HLA-A*02+ patient , wherein said cancer comprises cancer cells that overexpress a COL6A3 polypeptide and present at their surface in complex with an MHC class I molecule a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 40 , said method comprising administering to said patient an effective amount of activated antigen-specific CD8+ cytotoxic T cells to kill cancer cells , wherein said activated antigen-specific CD8+ cytotoxic T cells are produced by contacting in vitro CD8+ cytotoxic T cells with an antigen presenting cell presenting at its surface in complex with an MHC class I molecule a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 40 , wherein said cancer is selected from pancreatic cancer , small cell lung cancer , breast cancer , ovarian cancer , and esophageal cancer.2. The method of claim 1 , wherein the cytotoxic T cells produced by contacting CD8+ cytotoxic T cells with said antigen presenting cell are cytotoxic T cells autologous to the patient.3. The method of claim 1 , wherein the cytotoxic T cells produced by contacting CD8+ cytotoxic T cells with said antigen presenting cell are cytotoxic T cells obtained from a ...

CAR BASED IMMUNOTHERAPY

The disclosure provides chimeric antigen receptors (CARs), T cells comprising such CARs, nucleic acids that encode such CARS, and methods of use thereof, e.g., to treat cancer such as B cell malignancies. 121-. (canceled)22. A method for stimulating a T cell-mediated immune response to a target cell population or tissue in a mammal , the method comprisingadministering to a mammal an effective amount of a cell genetically modified to express a CAR, the CAR comprising an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the costimulatory signaling region comprises a CD28 signaling domain, a CD137 signaling domain and a CD27 signaling domain; and wherein the antigen binding domain is selected to specifically recognize the target cell population or tissue.2324-. (canceled)25. The method of claim 22 , wherein the genetically modified cell is an autologous T cell.26. The method of claim 22 , wherein the target cell population or tissue expresses a tumor antigen selected from the group consisting of CD19 claim 22 , CD20 claim 22 , CD22 claim 22 , ROR1 claim 22 , mesothelin claim 22 , CD33/IL3Ra claim 22 , c-Met claim 22 , PSMA claim 22 , Glycolipid F77 claim 22 , EGFRvIII claim 22 , GD-2 claim 22 , NY-ESO-1 TCR claim 22 , and MAGE A3 TCR.27. A method of treating a human with cancer claim 22 , the method comprising administering to the human a T cell genetically engineered to express a CAR claim 22 , wherein the CAR comprises an antigen binding domain claim 22 , a transmembrane domain claim 22 , a costimulatory signaling region claim 22 , and a CD3 zeta signaling domain claim 22 , wherein the costimulatory signaling region comprises a CD28 signaling domain claim 22 , a CD137 signaling domain and a CD27 signaling domain.28. The method of claim 27 , wherein the human is resistant to at least one chemotherapeutic agent.29. A method of generating a persisting population of genetically engineered T cells in ...

haNK CETUXIMAB COMBINATIONS AND METHODS

Contemplated cancer therapies comprise co-administration of aldoxorubicin with an immune therapeutic composition that preferably comprises a vaccine component and a cytotoxic cell component. 1. A method of treating a patient having a tumor , comprising:providing an immune therapeutic composition comprising a vaccine component and a cytotoxic cell component, and further providing a chemotherapeutic composition comprising aldoxorubicin; andadministering the immune therapeutic composition and the chemotherapeutic composition in a dose and schedule sufficient to treat the tumor.2. The method of claim 1 , wherein the vaccine component comprises at least one of a modified bacterium claim 1 , a modified yeast claim 1 , and a modified virus claim 1 , and wherein the vaccine component further comprises a recombinant nucleic acid encoding a tumor associated antigen.3. The method of claim 2 , wherein the vaccine component comprises at least two of a modified bacterium claim 2 , a modified yeast claim 2 , and a modified virus claim 2 , and wherein the vaccine component further comprises a recombinant nucleic acid encoding a tumor associated antigen.4. The method of any one of or claim 2 , wherein the tumor associated antigen is selected from the group consisting of brachyury claim 2 , MUC1 claim 2 , and CEA.5. The method of any one of the preceding claims claim 2 , wherein the cytotoxic cell component is at least one of a haNK cell and a T cell claim 2 , wherein the haNK cell or the T cell is genetically engineered to express at least one of a chimeric antigen receptor and a CD16 high-affinity variant.6. The method of any one of the preceding claims claim 2 , further comprising administering an antibody to the patient or a protein that interferes with or down-regulates checkpoint inhibition.7. The method of claim 6 , wherein the antibody is coupled to the cytotoxic cell component.8. The method of or claim 6 , wherein the antibody specifically binds to at least one of a growth ...

Methods and Compositions for Enhancing Vaccine Immune Responses

Provided herein are immunogenic compositions comprising a recombinant modified vaccinia virus Ankara (MVA) comprising a nucleic acid sequence encoding a CD40 ligand (CD4OL) and a nucleic acid sequence encoding a heterologous disease-associated antigen, wherein the immunogenic composition induces increases T-cell immune responses specific for the heterologous disease-associated antigen when administered to a human host, and related methods and uses.

De novo binding domain containing polypeptides and uses thereof

Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.

IN VIVO USE OF MODIFIED CELLS OF LEUKEMIC ORIGIN FOR ENHANCING THE EFFICACY OF ADOPTIVE CELL THERAPY

The present disclosure provides in vivo methods which employ modified cells of leukemic origin to enhance the efficacy of adoptive cell therapy. 1. A method for treating a disease or disorder in a subject in need thereof , comprising:administering to the subject a first composition comprising a modified cell of leukemic origin, wherein the modified cell is non-proliferating; andadministering to the subject a second composition comprising a modified immune cell, wherein the modified immune cell comprises an immune receptor.2. The method of claim 1 , wherein the modified cell:comprises at least one tumor antigen selected from the group consisting of WT-1, RHAMM, PRAME, MUC-1, p53, and Survivin;is CD34-positive, CD1a-positive, CD83-positive, and CD14-negative;further comprises a cell surface marker selected from the group consisting of DC-SIGN, Langerin, CD40, CD70, CD80, CD83, CD86, and any combination thereof;is CD40-positive, CD80-positive, and CD86-positive;comprises a costimulatory molecule, optionally wherein the costimulatory molecule is CD70;comprises an MHC class I molecule;comprises an MHC class II molecule;comprises an exogenous antigen or peptide fragments thereof, wherein the modified cell is capable of expressing the exogenous antigen, or is not capable of expressing the exogenous antigen;is loaded with an exogenous antigen or peptide fragments thereof, prior to its exhibiting a mature dendritic cell phenotype, during its transition of a mature dendritic cell phenotype, or after it exhibits a mature dendritic cell phenotype;{'b': '16', 'comprises a genetic aberration between chromosome 11p15.5 to 11p12, optionally wherein the genetic aberration encompasses about Mb of genomic regions; or'}is irradiated.39-. (canceled)10. The method of claim 2 , wherein the exogenous antigen:is a tumor-associated antigen (TAA) or a non-tumor-associated antigen;is provided in the form of a peptide, a nucleotide sequence, whole protein, or tumor lysate;is matched with the ...

Compositions and methods of treating cancer with chimeric antigen receptors

This disclosure relates to compositions and methods for treating cancer using armored chimeric antigen receptor cells.

Compositions and Methods for Enhancing the Stability of Transgenes in Poxviruses

Provided herein are recombinant poxviruses that are stable through successive passaging of the recombinant poxviruses. More particularly, the recombinant poxviruses comprise one or more modified nucleic acids encoding MUC1, CEA, and/or TRICOM antigens, wherein the recombinant poxviruses are stable through successive passaging. Also, provided herein are compositions and method related thereto.

PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF TUMORS EXPRESSING EGFR AND GM3 N-GLYCOLYL GANGLIOSIDE (NeuGcGM3)

The present invention relates to pharmaceutical compositions for the treatment of malignant tumors. Particularly those tumors that express EGFR and GM3 N-glycolyl ganglioside targets to enhance the therapeutic effect produced by separated therapies against these targets. The pharmaceutical compositions of the invention include antibodies and/or vaccines against each of the targets. Additionally the present invention relates to methods for applying the compositions of the invention.

Nant Cancer Vaccine

Cancer is treated using coordinated treatment regimens that uses various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting. 1. A method of treating cancer in a patient in need thereof , the method comprising administering to the patient a sequence of therapeutics , wherein the sequence comprises a platinum chemotherapeutic , Nab-paclitaxel , haNK cells , a means for binding PD-L1 , and IL-15 or IL-15N72D , wherein the means for binding PD-L1 is an antibody.2. The method of claim 1 , wherein the means for binding PD-L1 is avelumab.3. The method of claim 1 , wherein the IL-15N72D is ALT-803.4. The method of claim 3 , wherein the sequence is administered in a succession of cycles.5. The method of claim 4 , wherein the platinum chemotherapeutic is administered on day 1 of the cycle.6. The method of claim 5 , wherein the Nab-paclitaxel is administered on days 1 and 15 of the cycle.7. The method of claim 6 , wherein the haNK cells are administered on day 9 of the cycle.8. The method of claim 7 , wherein the platinum chemotherapeutic claim 7 , the avelumab claim 7 , the haNK cells claim 7 , and the Nab-paclitaxel are administered intravenously (IV) claim 7 , and wherein the ALT-803 is administered subcutaneously.9. The method of claim 8 , wherein the platinum chemotherapeutic is cisplatin.10. The method of claim 9 , wherein the cisplatin dose comprises 125 mg.11. The method of claim 10 , wherein the haNK dose comprises 2×10cells.12. The method of claim 11 , wherein the antibody dose comprises 10 mg/kg.13. The method of claim 12 , wherein the ALT-803 dose comprises 10 μg/kg.14. The method of claim 13 , wherein the sequence further comprises 5-fluorouracil (5-FU).15. The method of claim 14 , wherein the 5-FU dose comprises 400 mg/m claim 14 , administered by continuous IV infusion over at least 24 hours.16. The method of claim 15 , wherein the sequence further comprises ...

COMPOSITIONS AND METHODS OF TREATING CANCER AND INFECTIONS USING BACTERIOPHAGE AND ITS MUTANTS

Provided herein are vaccine composition comprising an antigen conjugated to a capsid, wherein the capsid comprises wild type or native sequence. Provided herein are also vaccine composition comprising an antigen conjugated to a capsid, wherein said capsid comprises at least one mutation, such as a non-natural mutation. Such compositions are useful in the treatment and prevention of pathogenic infections, inflammatory diseases, and neurodegenerative disease, and cancer, among others. 1. A vaccine composition comprising an antigen conjugated to a capsid , wherein said capsid comprises at least one non-natural mutation.2. The vaccine composition of claim 1 , wherein the capsid comprises at least one claim 1 , two claim 1 , three claim 1 , four claim 1 , five claim 1 , six claim 1 , seven claim 1 , eight claim 1 , nine claim 1 , ten claim 1 , eleven claim 1 , twelve claim 1 , thirteen claim 1 , fourteen claim 1 , fifteen claim 1 , sixteen claim 1 , seventeen claim 1 , eighteen claim 1 , nineteen claim 1 , or twenty mutations.3. The vaccine composition of claim 1 , wherein the at least one non-natural mutation is a disulfide bond mutation.4. The vaccine composition of claim 1 , wherein the antigen is selected from the group consisting of carbohydrate antigen claim 1 , peptide claim 1 , protein claim 1 , nucleic acid claim 1 , and organic molecular antigen.5. The vaccine composition of claim 4 , wherein the antigen is a carbohydrate antigen.6. The vaccine composition of claim 5 , wherein the carbohydrate antigen is selected from the group consisting of (a) Mucin1 (MUC1) claim 5 , (b) Mucin4 (MUC4) claim 5 , (c) Ganglioside GD2 (GD2) claim 5 , (d) Fucosyl Ganglioside GM1 (GM1) claim 5 , (e) acetylated GD2 claim 5 , (f) Ganglioside GD3 (GD3) claim 5 , (g) acetylated GD3 claim 5 , (h) Fucosyl Ganglioside GM2 (GM2) claim 5 , (i) Globo-H claim 5 , (j) Lewis A claim 5 , (k) Lewis Y claim 5 , (1) polysialic acid claim 5 , (m) sialyl-Lewis A claim 5 , (n) Tf claim 5 , (o) Tn ...

BRACHYURY DELETION MUTANTS, NON-YEAST VECTORS ENCODING BRACHYURY DELETION MUTANTS, AND THEIR USE

The invention provides Brachyury deletion mutant polypeptides, nucleic acids encoding the polypeptides, non-yeast vectors comprising the nucleic acids, non-yeast cells, and methods of use. 1. A method for inducing an immune response to Brachyury comprising administering to a subject an effective amount of (i) a nucleic acid encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 3 , (ii) a non-yeast vector comprising the nucleic acid of (i) , (iii) a non-yeast cell comprising (i) or (ii) , or (iv) a composition comprising any one of (i)-(iii) , thereby inducing the immune response , wherein the immune response comprises a Brachyury specific CD4+ T cell response.2. The method of claim 1 , wherein the immune response further comprises a Brachyury specific CD8 T cell response.3. The method of claim 1 , further comprising measuring the Brachyury specific CD4 T cell response.4. A method for treating or preventing cancer in a subject claim 1 , comprising administering to the subject an effective amount of (i) a nucleic acid encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 3 claim 1 , (ii) a non-yeast vector comprising the nucleic acid claim 1 , (iii) a non-yeast cell comprising (i) or (ii) claim 1 , or (iv) a composition comprising any one of (i)-(iii) claim 1 , thereby treating or preventing the cancer in the subject.5. The method of claim 1 , wherein the subject is human.6. The method of claim 1 , wherein the subject has cancer.7. The method of claim 6 , wherein the cancer is a breast cancer claim 6 , small intestine cancer claim 6 , stomach cancer claim 6 , kidney cancer claim 6 , bladder cancer claim 6 , uterus cancer claim 6 , ovarian cancer claim 6 , testes cancer claim 6 , lung cancer claim 6 , colon cancer claim 6 , prostate cancer claim 6 , chronic lymphocytic leukemia (CLL) claim 6 , a B cell lymphoma claim 6 , a Burkitt's lymphoma or a Hodgkin's lymphoma.8. The method of claim 1 , comprising administering to the subject a ...