Способы и композиции для лечения опухолей

Группа изобретений относится к медицине, а именно к онкологии, и может быть использована для лечения субъекта, страдающего от рака. Для этого применяют комбинацию ингибитора гистондезацетилазы (HDACi) и композицию вакцины, содержащей популяцию плюрипотентных клеток, которые были инактивированы, для получения лекарственного средства для одновременного, раздельного или последовательного введения. Группа изобретений также относится к способу получения популяции плюрипотентных клеток, которые были инактивированы. Использование данной группы изобретений показало, что вакцинация ксеногенными эмбриональными стволовыми клетками в сочетании с ингибитором гистондезацетилазы (вальпроевой кислотой) вызывает более высокий противоопухолевый ответ. 4 н. и 20 з.п. ф-лы, 9 ил., 4 пр.

СПОСОБ УЛУЧШЕНИЯ ФУНКЦИИ ИММУННЫХ КЛЕТОК И ОЦЕНКИ МУЛЬТИФУНКЦИОНАЛЬНОСТИ ИММУННЫХ КЛЕТОК

КОМБИНИРОВАННАЯ ТЕРАПИЯ ДЛЯ СТАБИЛЬНОГО И ДОЛГОВРЕМЕННОГО ПРИЖИВЛЕНИЯ ТРАНСПЛАНТАТА

... 1. Способ лечения субъекта, нуждающегося в несингенном клеточном или тканевом трансплантате, включающий:(a) трансплантацию субъекту дозы без-Т-клеточных незрелых гемопоэтических клеток, причем указанные без-Т-клеточные незрелые гемопоэтические клетки содержат меньше чем 5×10CD3Т-клеток на кг массы тела субъекта, и причем указанная доза содержит по меньшей мере приблизительно 5×10CD34+ клетки на кг массы тела субъекта; и впоследствии(b) введение субъекту терапевтически эффективного количества циклофосфамида, причем указанное терапевтически эффективное количество составляет 25-200 мг на кг массы тела, тем самым обеспечивая лечение субъекта.2. Способ по п. 1, дополнительно включающий:(i) кондиционирование субъекта в режиме кондиционирования сниженной интенсивности перед стадией (а); или(ii) кондиционирование субъекта с помощью in vivo Т-клеточной циторедукции перед стадией (а), и необязательно при котором указанную in vivo Т-клеточную циторедукцию осуществляют с помощью антител.3. Способ по ...

Polypeptides

Combined organ and hematopoietic cells for transplantation tolerance of grafts

An organ donor-derived composition of engineered hematopoietic cells comprising at least 1 x 106 CD34+ cells/kg recipient weight and at least 1 x 106 CD3+ T cells/kg recipient weight for use in organ transplantation to an HLA-mismatched recipient preferably allows withdrawal of immunosuppressive drugs without rejection. The administration of said composition of engineered hematopoietic cells comprises: (a) implanting an organ in a recipient of said organ transplantation; (b) treating said recipient of said organ transplantation with a non-myeloablative conditioning; (c) infusing said recipient of said organ transplantation with said composition of engineered hematopoietic cells as set forth in any of the preceding claims; and (d) maintaining said recipient of said organ transplantation on an immunosuppressive regimen for a period of time sufficient to develop a mixed chimerism for at least six months.

New particulate material, its preparation and its application, especially as a medicament

A particulate material for inducing immunity to cholera toxin comprises support particles provided with a first coating of a ganglioside having affinity for cholera toxin and a second coating of cholera toxin attached to said ganglioside coating. This particulate material can be used as an orally or parenterally administered medicine for humans to induce an immunity response to cholera toxin.

Method for the prevention of malaria

Method for the prevention of malaria

Method for the prevention of malaria.

Method for the prevention of malaria

Method for the prevention of malaria

PRODUCTION AND ISOLATION OF ANTIGEN-SPECIFIC TZELLEN

THERAPY STRATEGY FOR THE TREATMENT OF AUTOCIMMUNE DISEASES AND DEGENERATIVE ILLNESSES

IMMUNE MODULATION DEVICE FOR USE IN ANIMALS

CANCER IMMUNE THERAPY USING TUMOR CELLS COMBINES WITH LYMPHOZYTMISCHUNGEN

DIAGNOSIS AND TREATMENT OF AUTOCIMMUNE DISEASES

DIFFERENTIALLY EXPRIMIERTE LEISHMANIA GENES AND PROTEINS

Regulation of systemic immune responses utilizing soluble cd40

IMMUNOTHERAPY WITH IN VITRO-SELECTED ANTIGEN-SPECIFIC LYMPHOCYTES AFTER NONMYELOABLATIVE LYMPHODEPLETING CHEMOTHERAPY

Expansion of renewable stem cell populations using modulators of PI 3-kinase

Expansion of Renewable Stem Cell Populations

Use of an organ-specific self-pathogen for treatment of a non-autoimmune disease of said organ

RE-ACTIVATED T-CELLS FOR ADOPTIVE IMMUNOTHERAPY

Combined organ and hematopoietic cells for transplantation tolerance of grafts

Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Vaccines for the treatment of cancer and compositions for enhancing vaccine efficacy

The present invention relates to the treatment and prevention of cancer. The present invention relates to vaccines comprising solubilized components of cancer cells or cancer- associated cells. Moreover, the present invention also relates to methods of producing vaccines from biological samples comprising cancer cells or cancer-associated cells and using said vaccines for the treatment or prevention of cancer in subjects. The present invention also relates to methods of producing vaccines, in particular, autologous vaccines. The present invention also relates to therapeutic uses of mesenchymal stem cells and to methods of treatment and or prevention that comprise administering mesenchymal stem cells to a subject. The present invention also relates to methods of enhancing the efficacy of vaccines and methods for the treatment and prevention of cancer, and to compositions and kits suitable for use in the methods.

Anti-TLR4 Antibodies and Methods of Use Thereof

This invention relates generally to antibodies that specifically bind Toll-like Receptor 4 (TLR-4), and to methods of using the anti-TLR4 antibodies as therapeutics and to methods of using the anti TLR4 antibodies in methods of preventing transplant rejection and/or prolonging survival of transplanted biological material.

Multi-subtype FIV vaccines

VACCINE FOR PROPHYLAXIS AND THERAPY OF DERMATOPHYTOSIS IN VETERINARY AND HUMAN MEDICINE

The invention relates to a vaccine containing vaccination strains of dermatophytes, to the use of said vaccine for immunoprophylaxis and treatment of dermatophytosis and to suitable methods for producing said vaccine.

HUMAN PANCREATIC EPITHELIAL PROGENITOR CELLS AND METHODS OF ISOLATION AND USE THEREOF

... ²²²The invention discloses a substantially pure population of human pancreatic ²progenitor cells and methods of isolating and culturing the pancreatic ²progenitor cells. By carefully manipulating the microenvironment of the ²pancreatic progenitor cells, multiple passages are attainable wherein the ²pancreatic progenitor cells do not senesce and furthermore, are capable of ²becoming functional exocrine or endocrine cells. In addition, several methods ²of use of human pancreatic progenitor cells are disclosed herein.² ...

MODIFIED LEUKOTOXIN GENE AND PROTEIN

The present invention provides nucleic acid sequences encoding a modified leukotoxin protein, wherein the modification comprises the removal of nucleic acid sequences encoding amino acids within hydrophobic transmembrane domains of full length leukotoxin protein, preferably from Mannheimia haemolytica. The modified leukotoxin proteins are useful in vaccine compositions effective against Mannheimia haemolytica in animals.

COMPOSITIONS AND METHODS FOR THE THERAPY AND DIAGNOSIS OF OVARIAN CANCER

Compositions and methods for the therapy and diagnosis of cancer, particularly ovarian cancer, are disclosed. Illustrative compositions comprise one or more ovarian tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly ovarian cancer.

NEW PROSTATE CELL LINES

An increasingly aged population and better diagnosis has lead to an apparent increase in the prevalence of prostate cancer in men. There is an acute need to better understand the progression of this disease from its locally confined site of initiation to the end stage widely metastatic disease with attendant morbidity and mortality. It has historically been difficult to raise and maintain immortalised prostate cell lines in culture. We have derived a cell line selected from the group consisting of clones ONYCAP 1 and ONYCAP23. The cell lines are characterised as being prostate epithelial in origin.

THERAPEUTIC STRATEGY FOR TREATING AUTOIMMUNE AND DEGENERATIVE DISEASES

... ²²²Numerous diseases have been linked to the production of effector cells. The ²present invention relates to the realization that effector cells are cycling ²in these diseases. In addition, the present invention relates to the ²determination that regulator cells are cycling in degenerative diseases. Based ²on these realizations, the present invention provides methods for treating ²conditions such as autoimmune diseases, degenerative diseases, and graft-²versus-host disease. The present invention also relates to methods of ²determining when therapy should be administered to a patient.² ...

COMPOSITIONS AND METHODS FOR WT1 SPECIFIC IMMUNOTHERAPY

Compositions and methods for the therapy of malignant diseases, such as leukemia and cancer, are disclosed. The compositions comprise one or more of a WT1 polynucleotide, a WT1 polypeptide, an antigen-presenting cell presenting a WT1 polypeptide, an antibody that specifically binds to a WT1 polypeptide; or a T cell that specifically reacts with a WT1 polypeptide. Such compositions may be used, for example, for the prevention and treatment of metastatic diseases.

AMELIORATING OR THERAPEUTIC AGENT FOR CHRONIC PROSTATITIS, INTERSTITIAL CYSTITIS AND/OR URINATION DISORDERS

The purpose of the present invention is to provide a medicament which is useful for amelioration or treatment of chronic prostatitis, interstitial cystitis and/or urination disorders. Specifically, the present invention relates to a novel pharmaceutical use of an extract from inflamed tissue inoculated with vaccinia virus, and relates to an ameliorating or therapeutic agent for chronic prostatitis, interstitial cystitis and/or urination disorders, said agent containing the extract as an active ingredient. The medicament of the present invention containing the extract as an active ingredient is extremely useful as a highly effective and highly safe ameliorating or therapeutic agent for chronic prostatitis, interstitial cystitis and/or urination disorders.

ACELLULAR PRO-TOLEROGENIC COMPOSITIONS AND PROCESS FOR MAKING SAME

This invention relates to pro-tolerogenic preparations capable of increasing the level of regulatory T cells (Treg) and/or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. The pro-tolerogenic preparation is enriched in at least one species of miRNAs and is obtained by contacting two allogeneic leukocyte populations wherein at least one of the two populations is modified with a low-immunogenic biocompatible polymer. Acellular pro-tolerogenic compositions, process for making such composition as well as therapeutic uses of such compositions are also provided.

THERAPEUTICALLY ACTIVE PARTICULATE MATERIAL, ITS PREPARATION AND ITS USE AS A PHARMACEUTICAL.

Cell preparations which can be used in human therapy and method for obtaining them

The preparations consist of cells to which substances having pharmacological activity, e.g. substances capable of giving rise to antibody formation or of binding antibodies, are bound at the cell surface via a bridging agent. These preparations may be used as antigenic substances in vaccines, or for the preparation of hyperimmune serum. ...

REPLACEMENT OF CYTOTOXIC PRELIMINARY CONDITIONING BEFORE CELL BY THE IMMUNOTHERAPY

СПОСОБ ПОЛУЧЕНИЯ ПРОТИВООПУХОЛЕВОЙ ВАКЦИНЫ НА ОСНОВЕ ПОВЕРХНОСТНЫХ АНТИГЕНОВ ЭНДОТЕЛИАЛЬНЫХ КЛЕТОК

Согласно способу получения противоопухолевой вакцины с использованием эндотелиальных клеток живые эндотелиальные клетки подвергают витальному для клеток воздействию протеазы, отбирают высвободившиеся поверхностные антигены. При этом обработку живых эндотелиальных клеток протеазой повторяют с интервалами, необходимыми для восстановления клетками поверхностных антигенов, аккумулируют поверхностные антигены до достижения их дозы, необходимой для вакцинации, контролируют качество получаемой вакцины. Технический результат, достигаемый при использовании патентуемого изобретения, заключается в повышении эффективности лечения онкологических заболеваний за счет повреждения опухолевых сосудов путем преодоления иммунной толерантности организма к ЭК опухолевых сосудов. Имеется ввиду преодоление иммунной толерантности именно к активированным ЭК, что позволяет преимущественно вызывать повреждение иммунной системой именно опухолевых сосудов.

XENOGENIC VACCINE, OBTAINED FROM HEALTHY TISSUES, FOR OVERCOMING IMMUNE TOLERANCE WITH RESPECT TO OPUKhOLEASSOTsIIROVANNYKh ANTIGENS

CONTROL OVER TOXICITY IN CASE OF ANTITUMOR ACTIVITY OF CHIMERIC ANTIGENIC RECEPTORS

RECOMBINANT ARTIFICIAL ANTIGEN - PRESENTING CELLS FOR INCREASING THE NUMBER OF TUMOR - INFILTRATING LYMPHOCYTES

COMPOSITIONS AND METHODS RELATED TO MULTIMODAL THERAPEUTIC CELL SYSTEMS FOR CANCER INDICATIONS

Immunological agents - having pharmacologically active material attached to human, animal or microorganism cells

COMPOSITIONS AND METHODS RELATED TO MULTIMODAL THERAPEUTIC CELL SYSTEMS FOR CANCER INDICATIONS

Neoantígenos compartidos

...

SE DIVULGA AQUÍ EN UN ASPECTO UNA COMPOSICIÓN FARMACÉUTICA QUE COMPRENDE UNA PLURALIDAD DE PÉPTIDOS NEOANTIGÉNICOS Y UN PORTADOR FARMACÉUTICAMENTE ACEPTABLE, CADA PÉPTIDO NEOANTIGÉNICO QUE COMPRENDE UN NEOEPÍTOPO ESPECÍFICO A TUMOR CAPAZ DE UNIRSE A UNA PROTEÍNA HLA EN UN SUJETO, CADA NEOEPÍTOPO ESPECÍFICO A TUMOR COMPRENDE UNA MUTACIÓN ESPECÍFICA A TUMOR PRESENTE EN UN TUMOR, EN EL QUE (A) LA COMPOSICIÓN COMPRENDE PÉPTIDOS NEOANTIGÉNICOS QUE COMPRENDEN MUTACIONES ESPECÍFICAS A TUMOR PRESENTE EN POR LO MENOS 1% DE LO SUJETOS EN UNA POBLACIÓN DE SUJETOS QUE SUFREN DE CÁNCER; (B) LA COMPOSICIÓN COMPRENDE PÉPTIDOS NEOANTIGÉNICOS QUE COMPRENDEN NEOEPÍTOPOS ESPECÍFICOS A TUMORES QUE SE UNEN A PROTEÍNAS HLA PRESENTES EN POR LO MENOS 5% DE LO SUJETOS EN LA POBLACIÓN; Y (C) LA COMPOSICIÓN COMPRENDE POR LO MENOS UN PÉPTIDO NEOANTIGÉNICO CAPAZ DE PROVOCAR UNA RESPUESTA INMUNITARIA CONTRA UN TUMOR PRESENTE EN POR LO MENOS 5% DE LOS SUJETOS EN LA POBLACIÓN DE SUJETOS QUE SUFREN DE CÁNCER.

Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion

In some embodiments, compositions and methods relating to isolated artificial antigen presenting cells (aAPCs) are disclosed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-A/B/C, ICOS-L, and CD58, and wherein the one or more viral vectors comprise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and/or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and/or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

METHOD FOR ENHANCING IMMUNE CELL FUNCTION AND METHOD FOR ASSESSING IMMUNE CELL MULTIFUNCTIONALITY

INSULIN AUTOANTIGEN-SPECIFIC REGULATORY CD4+ T CELLS

Described herein are methods and compositions that can be used to prevent diabetes mellitus, or prevent or delay loss of residual -cell mass, providing a longer remission period and delaying the onset of diabetes related, usually progressive, complications at a later stage of the life. In addition, the methods described herein can be used to predict whether a subject, e.g., a subject with ongoing anti-insulin autoimmunity, will progress to T1DM, and to evaluate a subject's response to a therapeutic intervention.

METHOD OF PROLIFERATING LAK CELL

Methods of therapy effective for various cancers, immune deficiency diseases and infections, and methods of proliferation/activation of cells associated therewith, performed at costs such as those applicable to nonhuman animals. There is provided a method of proliferation/activation, comprising, in the stage of cell culture, adding a plant lectin, such as concanavalin A, and a growth factor having interleukin 2-like activity to the medium. Accordingly, αβ-type T cells associated with cellular immune for cancers, immune deficiency diseases and infections can be proliferated/activated on a preferential basis.

METHODS OF INDUCING DIFFERENTIATION IN EX VIVO EXPANDED STEM CELLS

Methods of differentiating ex vivo expanded stem cells in-tissue and in vivo are provided. Also provided are methods of treating individuals suffering from a disorder necessitating cell replacement or tissue replacement therapy using ex vivo expanded stem cells.

IMMUNE MODULATION DEVICE FOR USE IN ANIMALS

The present invention is directed to an implantable immune modulation device that is useful for modulating an immune response in mammals, comprising a plurality of fibers, within a porous shell. The fiber filling is loaded with single or multiple antigens, and optionally one or more biologically active compounds such as cytokines (e.g. lymphokines, chemokines etc.), attachment factors, genes, peptides, proteins, nucleotides, carbohydrates or cells depending on the application.

EXPANSION OF RENEWABLE STEM CELL POPULATIONS USING MODULATORS OF PI 3-KINASE

Ex vivo and in vivo methods of expansion of renewable stem cells using modulators of PI 3-kinase activity, expanded populations of renewable stem cells, and uses thereof.

MATERIALS AND METHODS FOR IMMUNIZING AGAINST FIV INFECTION

The subject invention pertains to methods and compositions for protecting feline animals from infection by FIV using immunogens derived from primate immunodeficiency viruses, including HIV and SIV. Methods for vaccinating feline animals with the subject vaccine compositions are described. Feline animals vaccinated according to the methods and compositions of the subject invention exhibit protective humoral and cellular immune responses to FIV when challenged with FIV. The subject invention further concerns methods and compositions for protecting humans and other animals against infection by immunodeficiency viruses, such as HIV and FIV.

NOVEL VACCINE FOR PROPHYLAXIS AND THERAPY IN VETERINARY AND HUMAN MEDICINE

The invention relates to a vaccine containing vaccination strains of dermatophytes, to the use of said vaccine for immunoprophylaxis and treatment of dermatophytosis and to suitable methods for producing said vaccine.

ANTITUMOR ANTIGEN AGAINST HTLV-1 TUMOR OR ANTIGEN EPITOPE THEREOF

A CTL-recognition antigen having an antitumor effect on HTLV-1 tumors such as ATL or its antigen epitope is screened to thereby provide immune response-inducible vaccines containing, as the active ingredient, the CTL-recognition antigen or its antigen epitope thus obtained or DNA encoding the same, etc. Spleen T cells originating in an immunologically normal rat having been immunized with an HTLV-I infected cell line are stimulated with a formalin-fixed HTLV-I infected cell line to thereby establish an HTLV-I-specific CTL cell line. Then the cytotoxic activity of the above HTLV-I-specific CTL cell line on target cells G14 having been sensitized with synthetic peptides, which are candidates for epitopes is measured, thereby identifying major epitopes GAFLTNVPY. Immunologically normal rats were immunized with these epitope synthetic peptides and adjuvants to thereby induce tumor antigen epitope-specific CTL. Thus, the proliferation of HTLV-I infected tumor cells can be inhibited in vivo.

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.

Use of an organ-specific self-pathogen for treatment of a non-autoimmune disease of said organ

An agent selected from: (a) a pathogenic self-antigen associated with a T-cell-mediated specific autoimmune disease of an organ; (b) a peptide which sequence is comprised within the sequence of (a); (c) a peptide obtained by modification of (b), by replacement of one or more amino acid residues by different amino acid residues, said modified peptide still being capable of recognizing the T-cell receptor recognized by the parent peptide but with less affinity; (d) a nucleotide sequence encoding (a), (b), or (c); and (e) T cells activated by a pathogenic self-antigen of (a), a peptide of (b), or a modified peptide of (c), can be used for treatment of a non-autoimmune disease, disorder or injury in said organ. For example, uveitogenic antigens or peptides thereof can be used for treatment of a non-autoimmune disease, disorder or injury in the eye.

Compounds and methods for treatment and diagnosis of chlamydial infection

Compounds and methods for the diagnosis and treatment of Chlamydial infection are disclosed. The compounds provided include polypeptides that contain at least one antigenic portion of a Chlamydia antigen and DNA sequences encoding such polypeptides. Pharmaceutical compositions and vaccines comprising such polypeptides or DNA sequences are also provided, together with antibodies directed against such polypeptides. Diagnostic kits containing such polypeptides or DNA sequences and a suitable detection reagent may be used for the detection of Chlamydial infection in patients and in biological samples.

Mesenchymal stem cells for prevention and treatment of immune responses in transplantation

A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of mesenchymal stem cells effective to reduce or inhibit host rejection of the transplant. The mesenchymal stem cells can be administered before, at the same time as, or after the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with mesenchymal stem cells.

METHODS FOR EXPANSION OR DEPLETION OF T-REGULATORY CELLS

The invention features methods of producing compositions enriched in Tregs and methods for treating immunological disorders using these compositions. The invention also features methods for producing compositions enriched in lymphocytes and depleted of Tregs and the use of these compositions in the treatment of proliferative disorders.

Materials and methods for immunizing against FIV infection

The subject invention pertains to methods and compositions for protecting feline animals from infection by FIV using immunogens derived from primate immunodeficiency viruses, including HIV and SIV. Methods for vaccinating feline animals with the subject vaccine compositions are described. Feline animals vaccinated according to the methods and compositions of the subject invention exhibit protective humoral and cellular immune responses to FIV when challenged with FIV.

INDUCTION OF IMMUNOLOGICAL TOLERANCE

ACTIVATED IMMUNOSTIMULATORY CELL COMPOSITION AND USES THEREOF

GPC3 APTAMERS AND VARIANTS AND USE THEREOF

INDUCTION OF IMMUNOLOGICAL TOLERANCE

PROJECTIONS OF MESENCHYMSTAMMZELLEN FOR PREVENTION AND TREATMENT OF IMMUNE ANSWERS IN TRANSPLANTS

PROSTATE GLAND ZELLINIEN AND THEIR USE

IL-2 INDEPENDENT T-CELLS OF THE CAT

HAPTEN MODIFIED TUMOR CELLS AND PROCEDURES FOR THE PRODUCTION AND THEIR USE

HUMAN PANKREATI EPITHELIAL MAIN CELLS, PROCEDURES FOR YOUR ISOLATION AND USES OF IT

METHOD FOR THE PREVENTION OF MALARIA

Cancer immunotherapy using tumor cells combined with mixed lymphocytes

Multi-subtype FIV vaccines

USE OF AN ORGAN-SPECIFIC SELF-PATHOGEN FOR TREATMENT OF A NON-AUTOIMMUNE DISEASE OF SAID ORGAN

Methods for improving graft acceptance in a recipient by administration of a cytokine profile altering agent

Modified leukotoxin gene and protein

Activation and protection of T-cells (CD4+ and CD8+) using an H2 receptor agonist and other T-cell activating agents

Human pancreatic epithelial progenitor cells and methods of isolation and use thereof

Compositions and methods related to multimodal therapeutic cell systems for cancer indications

The invention includes compositions and methods related to multimodal therapies, e.g., for treating a cancer. A multimodal therapy described herein provides and/or administers a plurality of agents that function in a coordinated manner to provide a therapeutic benefit to a subject in need thereof, e.g., a subject having a cancer.

Combined organ and hematopoietic cells for transplantation tolerance of grafts

Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

IPSC-based vaccine as a prophylactic and therapeutic treatment for cancer

In one embodiment, the application discloses a method for the treatment of cancer in a patient, the method comprises a vaccination of the patient with a vaccine, wherein the vaccine comprises an effective amount of mammalian pluripotent stem cells obtained from an embryonic source or obtained by reprogramming of somatic cells from the patient, wherein the vaccination comprising the step of administering a mammalian pluripotent stem cells to the patient in need thereof; and vaccine formulations for use in the treatment of cancer.

Method for enhancing immune cell function and method for assessing immune cell multifunctionality

Provided are: a method for enhancing immune cell function by activating ...

Platform for generating safe cell therapeutics

Provided herein are cytoplasts, compositions comprising cytoplasts, methods of using cytoplasts, and methods of treating a subject, such as providing benefits to a healthy or unhealthy subject, or treating or diagnosing a disease or condition in a subject. In some embodiments, methods of treating a subject include: administering to the subject a therapeutically effective amount of a composition comprising a cytoplast. Also, provided herein are compositions (e.g., pharmaceutical compositions) that include a cytoplast. Also, provided herein are kits comprising instructions for using the compositions or methods.

Methods and compositions for treating cancers

The inventors provide a new therapeutic strategy to treat cancers expressing embryonic antigens. Accordingly, the present invention relates to a method of treating a subject suffering from a cancer comprising a step of administration simultaneously, separately or sequentially to said subject a therapeutically amount of i) a population of derived engineered fetal stem cells carrying cancer associated fetal neo-antigen and ii) a compound selected from a group which activates immune response, as a combined preparation.

INACTIVATED TARGET CELLS, METHODS OF USING SAME AND VACCINES AND DIAGNOSTIC KITS CONTAINING SAME

INACTIVATED TARGET CELLS, METHODS OF USING SAME AND VACCINES AND DIGNOSTIC KITS CONTAINING SAME The present invention describes the inactivation of target cells by treatment of said cells with psoralens and irradiation with long wave length ultraviolet light. The inactivated cells are shown to be antigenic and are shown to be non-infective. These cells are useful as target antigens for in vitro assays of cellular immunity. Diagnostic kits containing the inactivated, target cells are prepared for use in serologic assays. Since the inactivated cells are immunogenic and non-infective, they are also useful as vaccines.

ANTIGENIC COMPOSITIONS

PLATFORM FOR GENERATING SAFE CELL THERAPEUTICS

Provided herein are cytoplasts, compositions comprising cytoplasts, methods of using cytoplasts, and methods of treating a subject, such as providing benefits to a healthy or unhealthy subject, or treating or diagnosing a disease or condition in a subject. In some embodiments, methods of treating a subject include: administering to the subject a therapeutically effective amount of a composition comprising a cytoplast. Also, provided herein are compositions (e.g., pharmaceutical compositions) that include a cytoplast. Also, provided herein are kits comprising instructions for using the compositions or methods.

COMPOSITIONS AND METHODS FOR WT1 SPECIFIC IMMUNOTHERAPY

Compositions and methods for the therapy of malignant diseases, such as leukemia and cancer, are disclosed. The compositions comprise one or more of a WT1 polynucleotide, a WT1 polypeptide, an antigen-presenting cell presenting a WT1 polypeptide, an antibody that specifically binds to a WT1 polypeptide; or a T cell that specifically reacts with a WT1 polypeptide. Such compositions may be used, for example, for the prevention and treatment of metastatic diseases.

METHODS FOR IMPROVING GRAFT ACCEPTANCE IN A RECIPIENT BY ADMINISTRATION OF A CYTOKINE PROFILE ALTERING AGENT

Methods for improving graft acceptance in a recipient by administration of a cytokine profile altering agent are disclosed. The methods involve biasing the cytokine response in a graft recipient to one dominated by Th2 cytokines either by increasing Th2 cytokine production or by decreasing Th1 cytokine production by administering an isolated cell and a cytokine profile altering agent to the subject to thereby promote acceptance of the graft in the subject.

PHARMACEUTICAL COMBINATIONS FOR TREATING TUMOR COMPRISING ANTI-CD19 ANTIBODY AND NATURAL KILLER CELL

Provided is a pharmaceutical combination comprising an antibody specific for CD19 and a natural killer cell, and a treatment method using the same. Such a pharmaceutical combination is capable of exhibiting synergistic therapeutic effects on a malignant tumor of B-cell origin such as non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and/or acute lymphoblastic leukemia.

METHODS AND COMPOSITIONS FOR TREATING CANCERS

The inventors provide a new therapeutic strategy to treat cancers expressing embryonic antigens. Accordingly, the present invention relates to a method of treating a subject suffering from a cancer comprising a step of administration simultaneously, separately or sequentially to said subject a therapeutically amount of i) a population of derived engineered fetal stem cells carrying cancer associated fetal neo-antigen and ii) a compound selected from a group which activates immune response, as a combined preparation.

METHODS FOR ISOLATING TUMOR-SPECIFIC IMMUNE CELLS FROM A SUBJECT FOR ADOPTIVE CELL THERAPY AND CANCER VACCINES

Disclosed are methods for the isolation of tumor-specific immune cells from subjects that have a malignant tumor and have received local administration of a composition comprising taxane particles to the malignant tumor, and use of such isolated immune cells in compositions for adoptive cell therapy and cancer vaccines.

FLAVIN N-OXIDES: NEW ANTI-CANCER AGENTS AND PATHOGEN ERADICATION AGENTS

Compounds comprising flavin N-oxides for treatments of solid tumors, non-solid tumor masses, leukemias, and non-small cell lung cancers and for eradicating contaminants in blood products. Methods of treating patients having solid type cancers comprising administering a therapeutically effective amount of flavin N-oxide to a subject in need of treatment and exposing the flavin n-oxide to an activator such that activation of the flavin N-oxide results in damage to the DNA in the cancer cells without substantial damage to the DNA of normal cells are also provided. Methods of using a flavin N-oxide as part of a combination therapy with chemotherapy, radiation therapy, or both are also provided. methods of reducing pathogenic bacterial or rival contamination in a composition comprising a) mixing the composition with an efficacious amount of flavin N-oxide and b) exposing the mixture of the composition and the flavin N- oxide to an activator for a period of time sufficient to activate the flavin ...

COMPOSITIONS AND METHODS RELATED TO MULTIMODAL THERAPEUTIC CELL SYSTEMS FOR CANCER INDICATIONS

The invention includes compositions and methods related to multimodal therapies, e.g., for treating a cancer. A multimodal therapy described herein provides and/or administers a plurality of agents that function in a coordinated manner to provide a therapeutic benefit to a subject in need thereof, e.g., a subject having a cancer.

Transfection of blood cells with mrna for immune stimulation and gene therapy

The present invention relates to a pharmaceutical composition containing blood cells or haemopoietic cells, e.g. red blood cells (erythrocytes), granulocytes, mononuclear cells (PBMCs) and/or blood platelets, in combination with a pharmaceutically acceptable excipient and/or vehicle, wherein the cells are transfected with at least one mRNA comprising at least one region coding for at least one antigen. The invention further discloses a method of preparing the aforesaid pharmaceutical composition and the use of blood cells transfected in this way for the preparation of drugs or pharmaceutical compositions for immune stimulation against the antigens encoded by the mRNA. The subjects according to the invention are used especially for the therapy and/or prophylaxis of carcinoses or infectious diseases and can also be employed in gene therapy.

Artificial cells

The present disclosure relates to various embodiments associated with artificial cells, particularly artificial antigen presenting cells, methods of making the same, methods of administering the same, computer systems relating thereto, computer-implemented methods relating thereto, and associated computer program products.

Artificial cells

The present disclosure relates to various embodiments associated with artificial cells, particularly artificial antigen presenting cells, methods of making the same, methods of administering the same, computer systems relating thereto, computer-implemented methods relating thereto, and associated computer program products.

Immunotherapeutic agent

The present invention is directed to adoptive immunotherapy using a lymphocyte in which an antigen-specific receptor and a bioactive material gene such as an IL-2 gene or a water-soluble TGF-beta receptor gene are transferred. The bioactive material is intensively secreted to, for example, a local site of a tumor, thereby reducing systemic side effects as much as possible, and the survival time of the lymphocyte is increased, thereby further improving the effect of the adoptive immunotherapy.

Dendritic Cell Compositions and Methods

Methods are provided for the production of dendritic cells from monocytes that have been incubated at a temperature of 1° C.-34° C. for a period of approximately 6 to 96 hours from the time they are isolated from a subject. After the incubation period, the monocytes can then be induced to differentiate into dendritic cells. Mature dendritic cells made by the methods of the invention have increased levels of one or more of CD80, CD83, CD86, MHC class I molecules, or MHC class II molecules as compared to mature dendritic cells prepared from monocytes that have not been held at 1° C.-34° C. for at least 6 hours from the time they were isolated from a subject. Dendritic cells made by the methods of the invention are useful for the preparation of vaccines and for the stimulation of T cells.

Sparc-derived tumor rejection antigenic peptides and medicaments comprising the same

It is an objective of the present invention to identify SPARC protein-derived peptides that are able to induce human killer T cells and helper T cells having cytotoxic activity to tumors, and to provide a means for carrying out a tumor immunotherapy of patients with various types of cancers overexpressing SPARC. The present invention provides a peptide of any of the following: (A) a peptide which consists of the amino acid sequence as shown in any one of SEQ ID NOS: 1 to 3; or (B) a peptide which consists of an amino acid sequence comprising a substitution or addition of one or several amino acids with respect to the peptide consisting of the amino acid sequence as shown in any one of SEQ ID NOS: 1 to 3, and which has capacity to induce cytotoxic (killer) T cells.

Immunologic compounds for prevention, protection, prophylaxis or treatment of immunological disorders, infections and cancer

The present invention provides for methods of treating a cancer patient. In one methods, cancer cells are harvested from a patient. A therapeutic amount of a rhodamine derivative is then added to the harvested cancer cells. The harvested cells and the rhodamine derivative are then irradiated with a suitable wavelength and intensity for the selective killing of the cancer cells. The irradiated cancer cells are then mixed with antigen presenting cells to form a mixture. The mixture of cancer and antigen presenting cells are then injected into the patient. The present invention also provides for methods of inhibiting or treating an immunological disorder, infection, or a cancer in an individual.

Methods for treating inflammation using b7-h4 polypeptides and fragments thereof

The invention provides novel B7-H3 and B7-H4 polypeptides useful for co-stimulating T cells, isolated nucleic acid molecules encoding them, vectors containing the nucleic acid molecules, and cells containing the vectors. Also included are methods of making and using these co-stimulatory polypeptides.

method of producing an antibody using a cancer cell

The present invention aims to provide a method for antibody preparation. The present invention is directed to a method for preparing an antibody-producing cell, which comprises the following steps: (1) transplanting metastatic cancer cells capable of expressing a target antigen into a non-human animal to ensure engraftment of the cancer cells in the animal; (2) immunizing the animal with the target antigen; and (3) collecting the antibody-producing cell from the immunized animal; as well as a method for preparing an antibody, which comprises collecting the antibody from the antibody-producing cell prepared by the above method.

Method for Inhibiting Scavenger Receptor-A and Increasing Immune Response to Antigens

Provided is a method for enhancing an immune response to a desired antigen in an individual. The method is performed by administering to the individual an agent capable of inhibiting class A macrophage scavenger receptor (SR-A) and optionally administering the desired antigen. Also provided is a method for enhancing an immune response to an antigen by administering to an individual a composition containing antigen presenting cells that are characterized by specifically inhibited SR-A. Substantially purified populations of mammalian dendritic cells characterized by specifically inhibited SR-A are also provided.

Foxm1 peptides and vaccines containing the same

The present invention provides isolated peptides having the amino acid sequence of SEQ ID NO: 34 or fragments thereof, which bind to HLA antigen and induce cytotoxic T lymphocyte (CTL). The present invention further provides peptides which include one, two, or several amino acid insertions, substitution or addition to the aforementioned peptides or fragments, but still have the cytotoxic T cell inducibility. Further provided are nucleic acids encoding any of these aforementioned peptides as well as pharmaceutical substances or compositions including any of the aforementioned peptides or nucleic acids. The peptides, nucleic acids, pharmaceutical substances or compositions of the present invention may be used for treating cancer or tumor.

Phosphopeptides as melanoma vaccines

We characterized a total of 175 HLA-DR-associated phosphopeptides using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing and comparative analysis. Many were derived from source proteins which may have roles in cancer development, growth and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome “fingerprints”. We generated HLA-DRβ1*0101-restricted CD4 + T cells specific for a phospho-MART-1 peptide identified in two melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen presenting cells as well as for intact melanoma cells. MHC II-restricted phosphopeptides recognizable by human CD4 + T cells are potential targets for cancer immunotherapy.

Compositions and methods to treat and control tumors

The present application is directed to non-coding RNA motifs that are used in conjunction with an antigen or without an antigen to induce, enhance or modulate an immune response that compromises a B cell and a T cell component.

Carbonic anhydrase i serving as novel antigen to be used for treatment of autoimmune diseases

The purpose of the present invention is to provide a method for treating autoimmune diseases. Disclosed is a method or the like for the treatment of autoimmune diseases, which utilizes an antigen-specific tolerogenic antigen presenting cell. Specifically disclosed are: a method for producing an antigen-specific tolerogenic antigen presenting cell, which is characterized by using carbonic anhydrase I; an immunogenic antigen presenting cell which is specific to carbonic anhydrase I; and a method or the like for the treatment of autoimmune diseases (especially inflammatory bowel diseases), which is characterized by using a tolerogenic antigen presenting cell which is specific to carbonic anhydrase I.

Methods of growing tumor infiltrating lymphocytes in gas-permeable containers

An embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal. Methods of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy are also provided.

Compositions for generating an antigen specific immune response

The present invention provides for the purposeful utilisation of the induction of senescence in eukaryotic cells for induction of an antigen specific immune response. Such cells can be normal cells, pre-malignant and malignant cells as well as virally or bacterially infected cells, for the generation of an immune response, preferably a cellular or humoral immune response comprising T-cells and/or B-cells, whose immune response is directed specifically against antigens from those cells in which senescence was induced and then comprises an immune response against the senescent cells itself as well as to the non-senescent counterparts harbouring the same antigens.

Tolerogenic synthetic nanocarriers for generating cd8+ regulatory t cells

Disclosed are synthetic nanocarrier methods, and related compositions, comprising administering MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen and immunosuppressants in order to generate tolerogenic immune responses against the antigen, such as the generation of antigen-specific CD8+ regulatory T cells.

Tolerogenic synthetic nanocarrier compositions with transplantable graft antigens and methods of use

Disclosed are synthetic nanocarrier compositions, and related methods, comprising APC presentable transplant antigens and immunosuppressants that provide tolerogenic immune responses (e.g., a reduction in CD8+ T cell proliferation and/or activity) specific to the APC presentable transplant antigens.

Tolerogenic synthetic nanocarriers to reduce cytotoxic t lymphocyte responses

Disclosed are synthetic nanocarrier compositions, and related methods, comprising MHC Class I-restricted and/or MHC Class II-restricted epitopes associated with undesired CD8+ T cell responses and immunosuppressants that provide tolerogenic immune responses against antigens that comprise the epitopes.

Tolerogenic synthetic nanocarriers

This invention relates, at least in part, to compositions comprising synthetic nanocarriers and immunosuppressants that result in immune suppressive effects. Such compositions can further comprise antigen and provide antigen-specific tolerogenic immune responses.

Methods and compositions for producing antigenic responses

The present inventions relates to methods of producing an antigenic response in which an antigen is contacted to an antigen-presenting cell, wherein the improvement comprises contacting the antigen-presenting cell with an A 1 adenosine receptor activating agent in an amount sufficient to increase the antigenic response of the antigen-presenting cell to the antigen. The present invention further provides methods, compositions, combination therapies, imaging techniques, and diagnostic kits that may improve the diagnosis, prognosis, and/or survival of cancer patients, pathogen-infected patients, and infectious or non-infectious immune-deficient patients.

Immunomodulating tumor necrosis factor receptor 25 (TNFR25) agonists, antagonists, and immunotoxins

Compositions and methods utilizing immunomodulating agents can either stimulate or indirectly augment the immune system or have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used to treat disease caused by asthma and chronic inflammation such as inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein are capable of inhibiting CD8 T cell-mediated cellular immune responses and can for example, mitigate organ or tissue rejection following a tissue transplantation.

T cell therapy for b cell lymphoma

Disclosed are methods and compositions for improving anti-tumor response and survivability in patients with cancer, such as non-Hodgkin lymphoma. In certain aspects, methods are provided for infusing lymphoma patients with T cells that are propagated ex vivo. Also provided are methods and compositions for propagating canine T cells ex vivo for infusion into cancer patients.

T cell receptor-deficient t cell compositions

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Kdr peptides and vaccines comprising the same

The present invention provides nonapeptides selected from peptides comprising the amino acid sequence of SEQ ID NO:2, 3, 5, 8, 11, or 12; nonapeptides or decapeptides selected from peptides comprising the amino acid sequence of SEQ ID NO:29, 30, 33, 34, 40, or 46; and peptides with cytotoxic T cell inducibility, in which one, two, or several amino acids are substituted or added to the above-mentioned amino acid sequences, as well as pharmaceuticals for treating or preventing tumors, where the pharmaceuticals comprise these peptides. The peptides of this invention can be used as vaccines.

Immune Effector Cells Pre-Infected with Oncolytic Virus

Compositions and methods are provided for the treatment of cancer. An immune effector cell population is pre-infected with an oncolytic virus. The combined therapeutic is safe and highly effective, producing an enhanced anti-tumor effect compared to either therapy alone. The methods of the invention thus provide for a synergistic effect based on the combined biotherapeutics.

Transplantable graft-specific induced tolerogenic dendritic cells and methods of use

Disclosed are transplantable graft-specific induced tolerogenic dendritic cells (itDCs), as well as related compositions and methods.

High affinity ny-eso t cell receptors

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC SEQ ID NO:126 peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a K D for the said peptide-HLA complex of less than or equal to 1 μM and/or have an off-rate (k off ) of 1×10 −3 S −1 or slower.

Methods of treatment using ex vivo expansion of cord blood t cells

Provided are methods of enhancing ex vivo proliferation of a T cell population, the methods comprising contacting the T cell population with IL-7 and anti-CD3/CD28 antibody to activate and expand the T cell population. Further provided are methods of generating an antigen-specific cytotoxic T cell population comprising priming a CD3/CD28-expanded T cell population against an antigen (e.g., a cancer cell) in the presence of at least one of IL-7, IL-12, and IL-15, or a combination thereof. Further provided are methods of treating T cell lymphopenia in a subject, comprising administering a CD3/CD28-expanded T cell population to the subject.

Induced tolerogenic dendritic cells to reduce systemic inflammatory cytokines

Disclosed are induced tolerogenic dendritic cells (itDCs), as well as related compositions and methods, for reducing systemic inflammatory cytokines.

Methods of cell culture for adoptive cell therapy

An improved method of culturing cells for cell therapy applications that includes growing desired cells in the presence of antigen-presenting cells and/or feeder cells and with medium volume to surface area ratio of up to 1 ml/cm 2 if the growth surface is not comprised of gas permeable material and up to 2 ml/cm 2 if the growth surface is comprised of gas permeable material. The desired cells are at a surface density of less than 0.5×10 6 cells/cm 2 at the onset of a production cycle, and the surface density of the desired cells plus the surface density of the antigen presenting cells and/or feeder cells are at least about 1.25×10 5 cells/cm 2 .

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.

Microbial delivery system

The present invention provides methods and compositions for treating or preventing allergic responses, particularly anaphylactic allergic responses, in subjects who are allergic to allergens or susceptible to allergies. Methods of the present invention utilize administration of microorganisms to subjects, where the microorganisms produce allergens and protect the subjects from exposure to the allergens until phagocytosed by antigen-presenting cells. Particularly preferred microorganisms are gram-negative bacteria, gram-positive bacteria, and yeast. Particularly preferred allergens are proteins found in foods, venoms, drugs and latex that elicit allergic reactions and anaphylactic allergic reactions in individuals who are allergic to the proteins or are susceptible to allergies to the proteins. The proteins may also be modified to reduce the ability of the proteins to bind and crosslink IgE antibodies and thereby reduce the risk of eliciting anaphylaxis without affecting T-cell mediated Th1-type immunity.

Tolerogenic Plasmacytoid Dendritic Cells Co-Expressing Cd8-Alpha And Cd8-Beta And Methods Of Inducing The Differentiation Of Regulatory T Cells Using Same

This invention discloses an unexpected discovery that plasmacytoid dendritic cells (pDCs) may be segregated into immunogenic or tolerogenic species based on novel biomarkers discovered herein. Exemplary biomarkers include CD8α + β + , CD8α + β − , CD8α − β − , C1q, and IL-9R. For example, pDCs with CD8α + β + , CD8α + β − are tolerogenic and CD8α − β − is immunogenic. Also disclosed are isolated pDCs, compositions comprising the pDCs, methods for isolating the pDCs, methods for treating immune-hyper-reactivity, such as airway hyper-reactivity, food allergy, asthma, and autoimmune disorders, by using compositions containing tolerogenic antigen presenting cells, preferably pDCs disclosed herein. Also disclosed are methods for identifying tolerogenic antigen presenting cells by using one or more novel biomarkers disclosed herein, including RALDH expression, CD8α, CD8βC1qa, C1qc, and IL-9R. Also disclosed are methods for inducing Treg cells by using the pDCs disclosed herein.

Compositions and methods including B lymphocyte cell line expressing membrane immunoglobulin different from secreted immunoglobulin

Compositions and methods are disclosed herein for producing one or more immunoglobulins in an isolated B lymphocyte cell line. An isolated cell line includes an isolated B lymphocyte cell line capable of expressing at least one exogenously incorporated membrane immunoglobulin reactive to a first antigen and at least one endogenous secreted immunoglobulin reactive to a second antigen.

Cells expressing Th1 characteristics and cytolytic properties

A novel cell type has been generated that has both Th1 characteristics and cytolytic activity. These Th1/killer cells are CD4+ cells purified from peripheral blood and manipulated to have Th1 characteristics such as production of IFN-gamma combined with cytolytic activity similar to cytotoxic T-cells (CTL). The CTL activity is targeted toward diseased cells, not normal cells. The cytolytic activity of the Th1/killer cells is mediated by Granzyme B-Perforin mechanism and results in apoptotic death of diseased cells. Methods of producing and using these Th1/killer cells include isolating CD4+ cells from peripheral blood, activating the CD4+ T-cells to form Th1/killer cells and administering these Th1/killer cells with the cytolytic activity to a patient wherein the Th1/killer cells are allogeneic to the patient.

Induced dendritic cell compositions and uses thereof

The invention provides, for example, compositions comprising induced tolerogenic dendritic cells which are capable of suppressing an antigen specific T cell-mediated immune response, and to methods of making and using the same. The invention also provides compositions comprising induced immunogenic dendritic cells and methods of making and using them.

Method for the treatment of obesity

The present invention relates to therapeutic compositions for treating or preventing obesity and obesity-related disorders in a subject using immunotherapy to target and eliminate adipocytes.

Molecular Vaccine Linking an Endoplasmic Reticulum Chaperone Polypeptide to an Antigen

This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.

Compositions and methods for producing dendritic cells

The present invention relates to compositions and methods for producing dendritic cells and particularly to compositions and methods for producing immature dendritic cells that are immunocompetent. We describe a method of producing dendritic cells by cultivation of monocytes, characterised by at least one of: pre-treatment of a tissue culture surface with at least one of: a substantially plasma-free and serum-free pre-treatment medium, a pre-treatment medium comprising heparin, and a pre-treatment medium comprising a protein solution; adsorption of monocytes using at least one of: a substantially plasma-free and serum-free adsorption medium; cultivation of monocytes using a substantially plasma-free and serum-free cultivation medium. We also describe compositions including the dentritic cells and uses of the dentritic cells.

Complex having tumor vaccine effect, and use thereof

The present invention provides a tumor cell-soluble TNF family member molecule complex containing a tumor cell and an isolated soluble TNF family member molecule, wherein the soluble TNF family member molecule is bound on a surface of the tumor cell such that it binds to a receptor of the TNF family member expressed on a surface of a cell other than the tumor cell, and stimulates the cell other than the tumor cell via the receptor, and a composition and a tumor vaccine, each containing the complex.

Immunomodulatory Methods and Systems for Treatment and/or Prevention of Hypertension

Immunomodulatory agents, T cell, compositions, methods and systems for treating and/or preventing hypertension and/or a condition associated thereto in an individual.

Compositions and Methods for the Treatment or Prevention of Hepatitis B Virus Infection

Disclosed are yeast-based immunotherapeutic compositions, hepatitis B virus (HBV) antigens, and fusion proteins for the treatment and/or prevention of HBV infection and symptoms thereof, as well as methods of using the yeast-based immunotherapeutic compositions, HBV antigens, and fusion proteins for the prophylactic and/or therapeutic treatment of HBV and/or symptoms thereof.

Chimeric receptors with 4-1bb stimulatory signaling domain

The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Pharmaceutical product comprising mite allergen extract(s) and a method for the manufacture thereof

The invention relates to a pharmaceutical product comprising an allergen extract or an allergoid thereof for the treatment and/or prevention of allergy and allergic asthma caused by house dust mites, which extract comprises at least one extract of mite bodies selected from the following groups a)-b): a) An extract of Der p mite bodies, and b) An extract of Der f mite bodies, and at least one extract of mite cultures selected from the following groups c)-g): c) An extract of Der p faecal particles, d) An extract of Der f faecal particles, e) An extract of Der f whole mite culture, f) An extract of an Der p whole mite culture, and g) a combination of extracts c) to f).

Human cytotoxic t-lymphocyte epitope and its agonist epitope from the non-variable number of tandem repeat sequence of muc-1

Novel MUC-1 epitopes outside the VNTR region are identified. In addition, the first agonist epitope of MUC-1 is described. The employment of agonist epitopes in peptide, protein and vector-based vaccine may well aid in the development of effective vaccines for a range of human cancers.

Method for Producing a Vaccine for the Treatment of Cancer

The present invention discloses a method for producing a haptenized vaccine from a tissue biopsy. The method includes obtaining a tissue biopsy, isolating the cells, irradiating the cells, haptenizing the cells, and cryopreserving the cells. The present invention also discloses a method for treating cancer using the vaccines produced by the methods described herein.

Method of vaccination

The present invention provides a method of expressing an antigenic molecule or a part thereof on the surface of an antigen-presenting cell, said method comprising introducing a molecule into the cell cytosol by photochemical internalisation, wherein said molecule, or a part thereof, is subsequently presented on the surface of said cell. Methods of vaccination comprising this method, together with compositions comprising said cells and uses involving said cells expressing antigenic molecules are also provided.

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).

Adoptive cell therapy with young t cells

The invention provides a method of promoting regression of a cancer in a mammal comprising (i) culturing autologous T cells; (ii) expanding the cultured T cells; (iii) administering to the mammal nonmyeloablative lymphodepleting chemotherapy; and (iv) after administering nonmyeloablative lymphodepleting chemotherapy, administering to the mammal the expanded T cells, wherein the T cells administered to the mammal are about 19 to about 35 days old and have not been screened for specific tumor reactivity, whereupon the regression of the cancer in the mammal is promoted.

Pharmaceutical compositions and methods to vaccinate against disseminated candidiasis and other infectious agents

The invention provides a vaccine including an isolated Als protein family member having cell adhesion activity, or an immunogenic fragment thereof, with an adjuvant in a pharmaceutically acceptable medium. The invention also provides a method of treating or preventing hematogenously disseminated or mucocutaneous candidiasis. A method of treating or preventing disseminated candidiasis also is provided that includes administering an effective amount of an isolated Als protein family member having cell adhesion activity, or an functional fragment thereof, to inhibit the binding or invasion of Candida to a host cell or tissue. The Als protein family member can be derived from a Candida strain selected from the group consisting of Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata and Candida parapsilosis and the Als protein family member includes Als1p, Als3p, Als5p, Als6p, Als7p or Als9p. Also provided is a method of treating or preventing Staphylococcus aureus infections.

Antitumor vaccination using allogeneic tumor cells expressing alpha (1,3)-galactosyltransferase

The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. Through ex vivo gene therapy protocols tumor cells are engineered to express an α(1,3)galactosyl epitope. The cells are then irradiated or otherwise killed and administered to a patient. The α galactosyl epitope causes opsonization of the tumor cell enhancing uptake of the opsonized tumor cell by antigen presenting cells which results in enhanced tumor specific antigen presentation. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.

Targeted therapeutic proteins

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Tumor lysate loaded particles

Dendritic cells containing tumor lysate loaded particles are prepared. The dendritic cells present tumor antigens to elicit the Major Histocompatibility Complex class I pathway and can be used as a vaccine to treat cancer, including ocular melanoma.

Methods and compositions for generating an immune response by inducing cd40 and pattern recognition receptor adapters

Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible pattern recognition receptor adapter, or adapter fragment, and CD40 activity. Also provided are nucleic acid compositions comprising sequences coding for chimeric proteins that include an inducible CD40 peptide and an inducible pattern recognition receptor adapter or adapter fragment.

Novel constructs for chimeric antigen receptors

The present disclosure pertains to immune cells comprising chimeric antigen receptors (CARs) and methods of using immune cells comprising CARs.

TARGET PEPTIDES FOR OVARIAN CANCER THERAPY AND DIAGNOSTICS

A set of target peptides are presented by HLA A*0201 on the surface of ovarian cancer cells. They are envisioned to among other things (a) stimulate an immune response to the proliferative disease, e.g., ovarian cancer, (b) function as immunotherapeutics in adoptive T-cell therapy or as a vaccine, (c) facilitate antibody recognition of tumor boundaries in surgical pathology samples, (d) act as biomarkers for early detection and/or diagnosis of the disease, and (e) act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex. 1. A composition comprising at least or about 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , or more synthetic target peptides , wherein each synthetic target peptide:(i) is about or at least 8, 9, 10, 11, 12, 13, 14 or 15 amino acids long; and(ii) comprises an amino acid sequence as set forth in any of SEQ ID NOs: 1-193,and further wherein said composition optionally stimulates a T cell-mediated immune response to at least one of the synthetic target peptides.2. The composition of claim 1 , wherein at least one of the synthetic target peptides comprises a substitution of a serine residue with a homo-serine residue.3. The composition of claim 1 , wherein at least one of the synthetic target peptides is a phosphopeptide that comprises a non-hydrolyzable phosphate group.4. The composition of claim 1 , wherein the composition is immunologically suitable for at least 60 to 88% of ovarian cancer patients.5. The composition of claim 1 , wherein the composition comprises at least 5 different target peptides.6. The composition of claim 1 , wherein the composition comprises at least 10 different target peptides.7. The composition of claim 1 , wherein the composition comprises at least 15 different target peptides.8. The composition of claim 1 , wherein at least one of the synthetic target peptides is capable of binding to an MHC class I molecule of the HLA-A*0201 allele.9. The composition of claim 1 , wherein the ...

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING GASTROINTESTINAL AND GASTRIC CANCER

A method of treating a patient who has gastric cancer, gastrointestinal cancer, colorectal cancer, pancreatic cancer, lung cancer, and/or renal cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has gastric cancer, gastrointestinal cancer, colorectal cancer, pancreatic cancer, lung cancer, and/or renal cancer. A method of treating a patient who has cancer includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the cancer. 1. A method of treating a patient who has gastric cancer , gastrointestinal cancer , colorectal cancer , pancreatic cancer , lung cancer , and/or renal cancer , comprising administering to said patient a composition comprising a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide , wherein said peptide comprises an amino acid sequence of TYKYVDINTF (SEQ ID NO: 58) , wherein the peptide is in a complex with an MHC molecule.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are derived from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , further comprising expanding T cells in vitro.6. The method of claim 1 , wherein the MHC molecule is a class I molecule.7. The method of claim 1 , wherein the composition further comprises an adjuvant.8. The ...

COMPOSITIONS, METHODS AND KITS FOR ELICITING AN IMMUNE RESPONSE

The present invention relates to compositions, methods, and kits for eliciting an immune response to at least one CMV antigen expressed by a cancer cell, in particular for treating and preventing cancer. CMV determination methods, compositions, and kits also are provided. 150-. (canceled)51. A method of eliciting in a subject an immune response to a cancer cell that expresses a cytomegalovirus (CMV) antigen , the method comprising:selecting a subject in need of treatment related to the presence of the cancer cell; andadministering to the subject a composition comprising a polynucleotide encoding a phosphoprotein unique long 83 (ppUL83; a/k/a pp65) or glycoprotein UL55 (gpUL55; a/k/a gB), or immunogenic fragments thereof wherein the composition, when administered to the subject, elicits an immune response to the cancer cell.52. The method of claim 51 , wherein the composition is provided in a therapeutically effective amount sufficient to treat a cancer associated with CMV in the subject.53. The method of claim 52 , wherein the cancer associated with CMV is a glioblastoma.54. The method of claim 52 , wherein the cancer associated with CMV is a breast cancer.55. The method of claim of claim 51 , wherein the composition comprises a polynucleotide encoding the phosphoprotein unique long 83 (ppUL83; a/k/a pp65) or immunogenic fragment thereof.56. The method of claim 55 , wherein the composition is provided in a therapeutically effective amount sufficient to treat a cancer associated with CMV in the subject.57. The method of claim 56 , wherein the cancer associated with CMV is a glioblastoma.58. The method of claim 56 , wherein the cancer associated with CMV is a breast cancer.59. The method of claim 55 , wherein the composition further comprises at least one adjuvant.60. The method of claim 59 , wherein the adjuvant is selected from at least one of: GM-CSF claim 59 , G-CSF claim 59 , IL-2 claim 59 , IL-4 claim 59 , IL-7 claim 59 , IL-12 claim 59 , IL-15 claim 59 , IL-21 ...

COMPOSITIONS, METHODS AND KITS FOR ELICITING AN IMMUNE RESPONSE

The present invention relates to compositions, methods, and kits for eliciting an immune response to at least one CMV antigen expressed by a cancer cell, in particular for treating and preventing cancer. CMV determination methods, compositions, and kits also are provided. 150-. (canceled)51. A method of eliciting in a subject an immune response to a cancer cell that expresses a cytomegalovirus (CMV) antigen , the method comprising:selecting a subject in need of treatment related to the presence of the cancer cell; andadministering to the subject a composition comprising a dendritic cell comprising a polynucleotide encoding a phosphoprotein unique long 83 (ppUL83; a/k/a pp65) or glycoprotein UL55 (gpUL55; a/k/a gB), or immunogenic fragments thereof wherein the composition, when administered to the subject, elicits an immune response to the cancer cell.52. The method of claim 51 , wherein the composition is provided in a therapeutically effective amount sufficient to treat a cancer associated with CMV in the subject.53. The method of claim 52 , wherein the cancer associated with CMV is a glioblastoma.54. The method of claim 52 , wherein the cancer associated with CMV is a breast cancer.55. The method of claim 51 , wherein the composition comprises a dendritic cell comprising a polynucleotide encoding the phosphoprotein unique long 83 (ppUL83; a/k/a pp65) or immunogenic fragment thereof.56. The method of claim 55 , wherein the composition is provided in a therapeutically effective amount sufficient to treat a cancer associated with CMV in the subject.57. The method of claim 56 , wherein the cancer associated with CMV is a glioblastoma.58. The method of claim 56 , wherein the cancer associated with CMV is a breast cancer.59. The method of claim 55 , wherein the composition further comprises at least one adjuvant.60. The method of claim 59 , wherein the adjuvant is selected from at least one of: GM-CSF claim 59 , G-CSF claim 59 , IL-2 claim 59 , IL-4 claim 59 , IL-7 ...

VECTOR CO-EXPRESSING VACCINE AND COSTIMULATORY MOLECULES

Compositions and methods for co-expressing a secretable vaccine protein (such as gp96-Ig) and T-cell co-stimulatory molecules from a single vector, among others, are provided herein. Materials and methods for using gp96-Ig vaccination and T-cell co-stimulation to treat a clinical condition (e.g., cancer) in a subject also are provided. 1. An expression vector comprising a first nucleotide sequence that encodes a secretable vaccine protein , and a second nucleotide sequence that encodes a T cell costimulatory fusion protein comprising TL1A-Ig , wherein the TL1A-Ig protein comprises an amino acid sequence having at least 97% to SEQ ID NO: 9 and enhances activation of antigen-specific T cells when administered to a subject.2. The expression vector of claim 1 , wherein the vector is a mammalian expression vector.3. The expression vector of claim 1 , wherein the secretable vaccine protein is a gp96-Ig fusion protein that lacks the gp96 KDEL (SEQ ID NO:3) sequence.4. The expression vector of claim 3 , wherein the Ig tag in the gp96-Ig fusion protein comprises the Fc region of human IgG1 claim 3 , IgG2 claim 3 , IgG3 claim 3 , or IgG4.512-. (canceled)13. The expression vector of claim 1 , wherein the expression vector comprises DNA.14. The expression vector of claim 1 , wherein the expression vector comprises RNA.1526-. (canceled)27. The expression vector of claim 1 , wherein the expression vector is incorporated into a virus or virus-like particle.28. The expression vector of claim 1 , wherein the expression vector is incorporated into a human tumor cell.29. The expression vector of claim 28 , wherein the human tumor cell is a cell from an established non-small cell lung carcinoma (NSCLC) claim 28 , bladder cancer claim 28 , melanoma claim 28 , ovarian cancer claim 28 , renal cell carcinoma claim 28 , prostate carcinoma claim 28 , sarcoma claim 28 , breast carcinoma claim 28 , squamous cell carcinoma claim 28 , head and neck carcinoma claim 28 , hepatocellular carcinoma ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST EPITHELIAL OVARIAN 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 eliciting an immune response in a patient who has cancer , comprising administering to said patient a composition comprising a population of activated T cells that kill cancer cells in the patient that present a peptide , wherein said peptide consists of the amino acid sequence of SEQ ID NO: 130 , 1 , 122 , 128 , 2 , 86 , 98 , 119 , 147 , 3-81 , 83 , 85 , 87-97 , 99-118 , 120 , 121 , 123-127 , 129 , 131-146 , or 148-549 , wherein said cancer is selected from the group consisting of ovarian cancer , non-small cell lung cancer , small cell lung cancer , kidney cancer , brain cancer , colon or rectum cancer , stomach cancer , liver cancer , pancreatic cancer , prostate cancer , leukemia , breast cancer , Merkel cell carcinoma , melanoma , esophageal cancer , urinary bladder cancer , uterine cancer , gallbladder cancer , and bile duct cancer.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are derived from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , further comprising expanding T cells in vitro.6. The method of claim 1 , wherein the peptide is in ...

Novel peptides and combination of peptides for use in immunotherapy against epithelial ovarian 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.

COMPOSITIONS AND METHODS OF TREATING ROOT AVULSION INJURY

A method of treating root avulsion injury in a subject in need thereof includes administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTPσ. 1. A method of treating root avulsion injury in a subject in need thereof , the method comprising:administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTPσ.2. The method of claim 1 , the therapeutic agent comprising a therapeutic peptide claim 1 , the therapeutic peptide having an amino acid sequence that is at least about 85% homologous to about 10 to about 20 consecutive amino acids of the wedge domain of PTPσ.3. The method of claim 1 , the therapeutic agent comprising a therapeutic peptide having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-25 claim 1 , 32 claim 1 , 63.4. The method of claim 1 , the therapeutic agent comprising a therapeutic peptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 32 and SEQ ID NO: 63.5. The method of claim 1 , the therapeutic agent comprising a therapeutic peptide having an amino acid sequence that is at least about 85% homologous to SEQ ID NO: 32 or SEQ ID NO: 63.6. The method of claim 8 , the therapeutic peptide including a conservative substitution of at least one of residue 4 claim 8 , 5 claim 8 , 6 claim 8 , 7 claim 8 , 9 claim 8 , 10 claim 8 , 12 claim 8 , or 13 of SEQ ID NO: 32 or residue 7 claim 8 , 8 claim 8 , 9 claim 8 , 10 claim 8 , 12 claim 8 , or 13 of SEQ ID NO: 63.7. The method of claim 2 , wherein the therapeutic agent includes a transport moiety that is linked to the therapeutic peptide and facilitates uptake of the therapeutic peptide by a nerve cell being treated.8. The method of claim 7 , wherein the transport moiety is an HIV Tat transport moiety.9. The method of claim 7 , wherein the therapeutic agent is administered systemically to the subject being treated.10. The ...

A*03 restricted peptides for use in immunotherapy against cancers and related methods

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.

Compositions and methods of treating cancer

The present invention provides compositions and methods for treating cancer, wherein the composition comprises: a. a population a cells comprising a dendritic cell/tumor cell fusion or a dendritic cell/extracellular vesicle fusion; and b. an indoleamine-2,3-dioxygenase (IDO) inhibitor and/or a hypomethylating agent (HMA).

A*03 RESTRICTED PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST CANCERS AND RELATED METHODS

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 peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 226 and SEQ ID NO: 252 to SEQ ID NO: 272 , and variant sequences thereof which are at least 88% homologous to SEQ ID NO: 1 to SEQ ID NO: 226 and SEQ ID NO: 252 to SEQ ID NO: 272 , and wherein said variant binds to molecule(s) of the major histocompatibility complex (MHC) and/or induces T cells cross-reacting with said variant peptide; and a pharmaceutical acceptable salt thereof , wherein said peptide is less than 30 amino acids in length2. The peptide or variant according to claim 1 , wherein said peptide has the ability to bind to an MHC class-I or -II molecule claim 1 , and wherein said peptide claim 1 , when bound to said MHC claim 1 , is capable of being recognized by CD4 and/or CD8 T cells.3. The peptide or variant thereof according to claim 1 , wherein the amino acid sequence thereof comprises a continuous stretch of amino acids according to any one of SEQ ID NO: 1 to SEQ ID NO: 226 and SEQ ID NO: 252 to SEQ ID NO: 272.4. The peptide or variant thereof according to claim 1 , wherein said peptide or variant thereof has an overall length of from 8 to 30 claim 1 , and optionally from 8 to 16 amino acids claim 1 , optionally wherein the peptide ...

CONDITIONAL SUPERAGONIST CTL LIGANDS FOR THE PROMOTION OF TUMOR-SPECIFIC CTL RESPONSES

What is described is a method of treatment of a patient with a tumor, comprising administering a cell responsive to a peptide comprising a tumor epitope, wherein the tumor epitope comprises an amino acid substitution in a tumor antigen. The tumor antigen is preferably selected from the group consisting of NYESO-I, NYESO-II, or MART-1, preferably SEQ ID NOS: 1-351, 361-376, and 392-401. 1. A method of treatment of a patient with a tumor , comprising administering a cell responsive to a peptide comprising a tumor epitope , wherein the tumor epitope comprises an amino acid substitution in a tumor antigen , and wherein the tumor antigen is selected from the group consisting of SEQ ID NOS: 1-351 , 361-376 , and 392-401.2. The method of claim 1 , wherein the tumor epitope comprises an amino acid substitution in a tumor antigen claim 1 , wherein the tumor antigen is SEQ ID NO: 144 or 228 claim 1 , and wherein the tumor epitope comprises a sequence selected from the group consisting of SEQ ID NOS: 362-365 and 368-376.3. The method of claim 2 , wherein the tumor antigen is SEQ ID NO: 144 claim 2 , and wherein the tumor epitope comprises a sequence selected from the group consisting of SEQ ID NOS: 368-376.4. The method of claim 3 , wherein the tumor epitope comprises a sequence consisting of SEQ ID NOS: 372 claim 3 , 374 claim 3 , or 375.5. The method of claim 2 , wherein the tumor antigen is SEQ ID NO: 228 claim 2 , and the tumor epitope comprises a sequence selected from the group consisting of SEQ ID NOS: 362-365.6. The method of claim 5 , wherein the tumor antigen is SEQ ID NO: 228 claim 5 , and the tumor epitope comprises a sequence selected from the group consisting of SEQ ID NOS: 362 claim 5 , 363 or 365.7. The method of claim 1 , wherein the tumor epitope comprises a multiplicity of sequences selected from the group consisting of SEQ ID NOS: 362-365 and 368-376.8. The method of claim 7 , wherein the tumor epitope comprises a multiplicity of sequences selected from the ...

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 ...

COMPOSITIONS AND METHODS FOR COMBINATION THERAPY WITH DENGUE VIRUS AND DENDRITIC CELLS

Described herein are compositions and methods for treating cancer through the combination of tumor antigen-pulsed dendritic cells and . The combination of the two forms of therapeutic intervention provides enhanced tumor cell reduction compared to either alone. The cancer targeted by compositions and methods described herein may be a solid cancer or blood cancer. 1. A method for treating cancer in a subject in need thereof , comprising:(a) incubating dendritic cells (DCs) with at least one tumor cell antigen;{'i': 'Dengue Virus', '(b) administering a Type 2 serotype strain DENV-2 #1710 to a subject; and'}(c) administering the DCs to the subject.2. The method of claim 1 , wherein the at least one tumor cell antigen is from a solid cancer cell or a blood cancer cell from the subject.3. The method of claim 2 , wherein the blood cancer leukemia or lymphoma.4. The method of claim 2 , wherein the solid cancer is melanoma claim 2 , breast claim 2 , prostate claim 2 , or brain cancer.5. The method of claim 1 , wherein the DCs or the at least one tumor cell antigen are from the subject.6. The method of claim 1 , wherein the DCs and the at least one tumor cell antigen are from the subject.7. The method of claim 1 , wherein the DCs are pulsed with the at least one tumor cell antigen.8. The method of claim 1 , wherein the at least one tumor cell antigen is a peptide.9Dengue Virus. The method of claim 1 , wherein the Type 2 serotype strain DENV-2 #1710 is present in an amount sufficient to induce a systemic infection.10. The method of claim 1 , wherein the DCs are administered after the subject's temperature reaches 38.5 degrees Celsius.11. The method of claim 1 , wherein the DCs are mature DCs capable of antigen uptake.12. A method for treating cancer in a subject in need thereof claim 1 , comprising:(a) lysing a tumor tissue from a subject to form a lysis product comprising apoptotic or necrotic bodies;(b) incubating dendritic cells (DCs) with the lysis product;{'i': 'Dengue ...

Compositions and Methods for Treating Immunological Dysfunction

The present invention is directed to methods of lymphotherapy to treat cancer, infection and autoimmune disease. 1. A ghost cell trainer (GHT) , wherein said GHT comprises a plasma membrane having:a. a plurality of MEW molecules; andb. a plurality of a protein of interest, wherein the protein is glycosylphosphatidylinositol(GPI) anchored on the cell surface.2. The GHT of claim 1 , wherein said GHT is of human claim 1 , canine claim 1 , feline murine or equine origin.3. The GHT of claim 1 , wherein the GPI anchored protein of interest is within a lipid raft.4. The GHT of claim 1 , wherein the MEW molecules are glycosylphosphatidylinositol (GPI) anchored on the cell surface within a lipid raft.5. The GHT of claim 1 , wherein the MEW molecules are HLA-Cw*3 and/or HLA-Cw*5.6. The GHT of claim 1 , wherein the protein of interest is a one or more co-stimulatory molecules.7. The GHT of claim 6 , wherein the co-stimulatory molecule is CD80 claim 6 , CD86 claim 6 , CD137 claim 6 , IL-15 claim 6 , CD28 claim 6 , IL-21 claim 6 , IL-2 claim 6 , IFN-gamma claim 6 , IL-10 claim 6 , IL-12 claim 6 , TGF-beta claim 6 , CD40L claim 6 , IL-4 claim 6 , or CD64.8. The GHT of claim 1 , wherein said GHT is derived from a primary cell or an immortalized cell.9. A ghost cell (GHC) claim 1 , wherein said cell comprising the following characteristics:a. is substantially free of all intracellular components; i. a plurality of MHC molecules;', 'ii. a plurality of a protein of interest, wherein the protein is glycosylphosphatidylinositol(GPI) anchored on the cell surface., 'b. has a plasma membrane having10. A method of producing a ghost cell (GHC) by lysing the GHT of to form a cell that is substantially free of all intracellular components.11. The method of claim 10 , wherein said lysing is by pH claim 10 , temperature claim 10 , chemical claim 10 , physical claim 10 , hypotonic or hypertonic means.12. A method of producing a ghost cell (GHC) comprising:a. transfecting a cell expressing an MHC ...

METHODS FOR PROFILING THE T CELL REPERTOIRE

The present disclosure relates to methods for profiling subject specific and personalized T cell receptor (TCR) repertoires using a single-cell sequencing method. More particularly, disclosed are methods for determining binding of T cell receptors to subject specific neoantigens. In addition, the techniques herein may identify the antigenic targets of T cell receptors in the context of tumor neoantigens. Moreover, the present disclosure enables the discovery of T cell targets in numerous diseases, with implications for understanding the basic mechanisms of the mammalian immune response and for developing antigen-specific diagnostic markers and therapies. Finally, cloned TCRs can be used to formulate personalized immunotherapies for those inflicted with a disease, such as cancer. 1. A method of identifying at least one subject specific T cell receptor pair expressed on a single T cell and preparing a subject-specific immunogenic composition that includes the at least one T cell receptor , wherein the subject has a tumor and the at least one subject-specific T cell receptors are specific to the subject and the subject's tumor , said method comprising:identifying TCR pairs from single tumor specific T cells from the subject; andformulating the subject-specific immunogenic composition, wherein the immunogenic composition comprises one or more T cells each expressing a single tumor-specific TCR pair identified from the subject.2. A method of identifying at least one subject specific T cell receptor pair expressed on a single T cell and preparing a subject-specific immunogenic composition that includes the at least one T cell receptor , wherein the subject has a tumor and the at least one subject-specific T cell receptors are specific to the subject and the subject's tumor , said method comprising:identifying TCRs from single T cells obtained from the subject, wherein the T cells are specific to subject-specific neoantigens;formulating the subject-specific immunogenic ...

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 OF INDUCING AN IMMUNE RESPONSE TO HEPATITIS C VIRUS

The present disclosure provides methods for inducing an immune response to hepatitis C virus (HCV) in an individual. The present disclosure provides methods for treating an HCV infection in an individual. 1. A method of inducing an immune response in an individual to a hepatitis C virus (HCV) protein , the method comprising administering to the individual an effective amount of an immunogenic composition comprising an adenoviral nucleic acid or an adenovirus polypeptide.2. The method of claim 1 , wherein the adenoviral nucleic acid or adenovirus polypeptide is administered via an oral claim 1 , intranasal claim 1 , subcutaneous claim 1 , transdermal claim 1 , intratracheal claim 1 , rectal claim 1 , intramuscular or parenteral route of administration.3. The method of any one of - claim 1 , wherein the adenoviral nucleic acid or adenovirus polypeptide is administered multiple times.4. The method of claim 3 , wherein the multiple administrations comprise a first administration wherein the adenoviral nucleic acid or adenovirus polypeptide is a first adenovirus serotype or subtype claim 3 , and at least a second administration wherein the adenoviral nucleic acid or adenovirus polypeptide is a second adenovirus serotype or subtype.5. The method of any one of - claim 3 , wherein said immune response comprises a humoral and/or a cellular immune response.6. The method of any one of - claim 3 , wherein the adenoviral nucleic acid is a full-length adenovirus nucleic acid or an adenovirus nucleic acid comprising a deletion.7. The method of any one of - claim 3 , wherein the adenoviral nucleic acid does not encode a non-adenovirus polypeptide.8. The method of any one of - claim 3 , wherein the adenoviral nucleic acid comprises a nucleotide sequence encoding one or more HCV polypeptides.9. The method of any one of - claim 3 , wherein the adenoviral nucleic acid comprises a nucleotide sequence encoding an antigen associated with a pathogen other than HCV or comprises a nucleotide ...

DNA VECTOR AND TRANSFORMED TUMOR CELL VACCINES

Customized whole cell cancer vaccines can be produced from autologous (ex vivo or in situ) or allogeneic human or veterinary patient cell lines. Cells are transformed with DNA that expresses an Emm protein on the cell surface and cytosol. Treatment of cancer patients with an Emm vector vaccine induces an immunologic response to the cancer by enhancing immunogenicity of a tumor. Emm vaccines can be used in patients where the cancer is not identified due to lower tumor burden or used to treat a specific cancer and subsequently treat for a second type that may have arisen through metastasis. 1. A method for preparing a membrane anchoring protein , comprising:{'i': 'streptococcus', 'inserting a first DNA encoding the amino acid sequence of SEQ ID NO: 7 into the N-terminal signal region of a DNA encoding an M serotype 55 group A protein;'}inserting a second DNA encoding the amino acid sequence of SEQ ID NO: 9 into the C-terminal anchor region of the DNA encoding said protein;wherein the encoded protein expressed from the modified DNA is a membrane anchoring protein.2streptococcus. The method of wherein the M serotype 55 group A protein is a gram positive bacterial cell wall protein.3Streptococcus.. The method of wherein the gram positive bacterial wall protein is from a serotype of group A4. The method of wherein the encoded protein has the amino acid sequence of SEQ ID NO: 5.5. The method of wherein the membrane anchoring protein anchors to a cell membrane.6. The cell membrane of which is a eukaryotic membrane.7. The cell membrane of which is a prokaryotic membrane. This application is a divisional of U.S. application Ser. No. 15/837,965, filed Dec. 11, 2017, now U.S. Pat. No. 10,391,158, which is a continuation-in-part of U.S. application Ser. No. 15/418,798, filed Jan. 30, 2017, now U.S. Pat. No. 9,839,680, which is a divisional of U.S. application Ser. No. 15/110,248, filed Jul. 7, 2016, now U.S. Pat. No. 9,555,088, which is the U.S. national stage application of ...

HEAT SHOCK PROTEIN-BINDING PEPTIDE COMPOSITIONS AND METHODS OF USE THEREOF

Provided are polypeptides and compositions comprising novel HSP-binding peptides. Such polypeptides and compositions are particularly useful as immunotherapeutics (e.g., cancer vaccines). Also provided are methods of inducing a cellular immune response using such polypeptides and compositions, methods of treating a disease using such polypeptides and compositions, kits comprising such polypeptides and compositions, and methods of making such compositions. 1. An isolated polypeptide comprising a heat shock protein (HSP)-binding peptide comprising the amino acid sequence of XLXLTX(SEQ ID NO: 1) , wherein Xis W or F; Xis R or K; and Xis W , F , or G.2. The isolated polypeptide of claim 1 , wherein the HSP-binding peptide comprises the amino acid sequence of:{'sub': 1', '2', '3', '1', '2', '3, '(a) NXLXLTX(SEQ ID NO: 2), wherein Xis W or F; Xis R or K; and Xis W, F, or G;'}{'sub': 1', '2', '1', '2, '(b) WLXLTX(SEQ ID NO: 3), wherein Xis R or K; and Xis W or G; or'}{'sub': 1', '2', '1', '2, '(c) NWLXLTX(SEQ ID NO: 4), wherein Xis R or K; and Xis W or G.'}3. The isolated polypeptide of claim 1 , wherein:(a) the HSP-binding peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5-12, 98-113, 207, and 212;(b) the amino acid sequence of the HSP-binding peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 5-12, 98-113, 207, and 212:(c) the HSP-binding peptide comprises the amino acid sequence of SEQ ID NO: 6; and/or(d) the amino acid sequence of the HSP-binding peptide consists of the amino acid sequence of SEQ ID NO: 6.46-. (canceled)7. An isolated polypeptide comprising an HSP-binding peptide comprising the amino acid sequence of NWXXXXX(SEQ ID NO: 232) claim 1 , wherein Xis L or I; Xis L claim 1 , R claim 1 , or K; Xis L or I; Xis T claim 1 , L claim 1 , F claim 1 , K claim 1 , R claim 1 , or W; and Xis W or K.8. The isolated polypeptide of claim 7 , wherein the HSP-binding peptide comprises an ...

MESOTHELIN CHIMERIC ANTIGEN RECEPTOR (CAR) AND ANTIBODY AGAINST PD-L1 INHIBITOR FOR COMBINED USE IN ANTICANCER THERAPY

Provided are compositions for use in methods for treating diseases associated with expression of mesothelin comprising administering a cell that expresses a chimeric antigen receptor (CAR) specific to mesothelin in combination with a PD-L1 inhibitor. 1. A method of treating a subject having a disease associated with mesothelin expression , comprising administering to the subjecti) a cell, e.g., a population of immune effector cells, comprising, e.g., expressing, a chimeric antigen receptor (CAR), wherein the CAR comprises a mesothelin binding domain, a transmembrane domain, and an intracellular signaling domain; andii) a PD-L1 inhibitor, wherein the PD-L1 inhibitor is administered prior to administration of the cell comprising a CAR.2. The method of claim 1 , wherein the CAR-expressing cell and the PD-L1 inhibitor is administered for a treatment interval claim 1 , and wherein the treatment interval comprises a single dose of the PD-L1 inhibitor and a single dose of the CAR-expressing cell.3. The method of claim 2 , wherein the treatment interval is initiated upon administration of the dose of the PD-L1 inhibitor and completed upon administration of the dose of the CAR-expressing cell.4. The method of or claim 2 , wherein the treatment interval further comprises one or more claim 2 , e.g. claim 2 , 1 claim 2 , 2 claim 2 , 3 claim 2 , 4 claim 2 , or 5 or more claim 2 , subsequent doses of the PD-L1 inhibitor.5. The method of any of - claim 2 , wherein the dose of the CAR-expressing cell is administered at least 2 days claim 2 , 3 days claim 2 , 4 days claim 2 , 5 days claim 2 , 6 days claim 2 , 7 days claim 2 , or 2 weeks after the dose of PD-L1 inhibitor is administered.6. The method of claim 5 , wherein the dose of the CAR-expressing cell is administered 2 days after the dose of the PD-L1 inhibitor is administered.7. The method of claim 1 , wherein the CAR-expressing cell and the PD-L1 inhibitor is administered for a treatment interval claim 1 , wherein the ...

THERAPEUTIC CANCER VACCINES DERIVED FROM A NOVEL DENDRITIC CELL LINE

The invention is in the field of medical sciences. It provides means and methods for the treatment of cancer. More in particular, it provides cells and cell lines that can be developed into fully functional dendritic cells. These cells endogenously express cancer-specific antigens, which makes them particularly suited for the treatment of different kinds of cancer. More in particular, the invention relates to a precursor cell line for dendritic cells called DC-One as deposited at the DSMZ under accession number DSMZ ACC3189 on Nov. 15, 2012. 1. (canceled)2. A method for obtaining mature dendritic cells , the method comprising:incubating a precursor cell line as deposited at the DSMZ under accession number DSMZ ACC3189 on Nov. 15, 2012, under conditions that allow differentiation of the progenitor cells into immature dendritic cells; andincubating the immature dendritic cells under conditions that allow maturation of the immature dendritic cells into mature dendritic cells.3. A method for obtaining mature dendritic cells , the method comprising:incubating a precursor cell line as deposited at the DSMZ under accession number DSMZ ACC3189 on Nov. 15, 2012, under conditions that allow differentiation of the progenitor cells into immature dendritic cells; andincubating the immature dendritic cells under conditions that allow maturation of the immature dendritic cells into mature dendritic cells; andaltering the phenotype of the mature dendritic cells by introducing genetic material into the cells and/or by knocking out endogenous genes of the cells.4. Mature dendritic cells obtained by the method according to .5. A medicament comprising the mature dendritic cells of .6. A method for the treatment of cancer claim 4 , the method comprising:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, 'administering to a subject suffering from cancer the mature dendritic cells of .'}7. The method according to claim 6 , wherein the cancer is acute myeloid leukemia (AML).8. A therapeutic ...

Novel peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (hcc) 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. In particular, the present invention relates to several novel peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses or as targets for the development of pharmaceutically/immunologically active compounds and cells.

DENDRITIC CELL COMPOSITION

The present invention contemplates dendritic cell compositions. The dentritic cell compositions employ MHC class-II targeting signals fused to an antigen or fragment thereof to obtain MHC II presentation of the antigen or fragment thereof. In particular, the invention refers to a dendritic cell vaccine comprising dendritic cells expressing a MHC class-II targeting signal fused to an antigen or fragment thereof. Dendritic cell vaccines for the stimulation of an immune response against melanoma-associated antigen are also described. 1. Dendritic cell composition comprising dendritic cells expressing at least one fusion protein comprisingat least one antigen or a fragment thereof,an endoplasmatic reticulum (ER)-translocation signal sequence preceding the N-terminus of the antigen, anda transmembrane and cytoplasmic domain comprising an endosomal/lysosomal targeting sequence following the C-terminus of the antigen.2. Dendritic cell composition according to claim 1 ,wherein the dendritic cell composition further comprises dendritic cells expressing at least one antigen or a fragment thereof wherein the antigen is not fused to a targeting signal sequences that promotes the MHC II presentation of the antigen or fragment thereof.3. Dendritic cell composition according to or claim 1 , wherein the targeting signal sequence that promotes the MHC II presentation is at least one selected from the group consisting ofan endoplasmatic reticulum (ER)-translocation signal sequence preceding the N-terminus of the antigen, anda transmembrane and cytoplasmic domain comprising an endosomal/lysosomal targeting sequence following the C-terminus of the antigen.4. Dendritic cell composition according to any one of the preceding claims claim 1 , wherein the fusion protein and the antigen are transiently or stably expressed claim 1 , preferably stably expressed.5. Dendritic cell composition according to claim 4 , wherein the transient expression is carried out by introducing ivt-RNA.6. ...

Vector co-expressing vaccine and costimulatory molecules

Compositions and methods for co-expressing a secretable vaccine protein (such as gp96-Ig) and T-cell co-stimulatory molecules from a single vector, among others, are provided herein. Materials and methods for using gp96-Ig vaccination and T-cell co-stimulation to treat a clinical condition (e.g., cancer) in a subject also are provided.

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS OF THE BLOOD, IN PARTICULAR CHRONIC LYMPHOID LEUKEMIA (CLL)

The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to several novel peptide sequences and their variants derived from HLA class I and HLA class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells , which present a peptide consisting of the amino acid sequence selected from the group consisting of from SEQ ID NO: 2 to SEQ ID NO: 76 and from SEQ ID NO: 78 to SEQ ID NO: 1016 , wherein said cancer is selected from the group consisting of chronic lymphoid leukemia (CLL) , acute myelogenous leukemia (AML) , adrenal gland adrenal cortical adenoma , bone giant cell tumor of bone , bone non-ossifying fibroma , breast carcinoma , colon adenocarcinoma , non-Hodgkin's lymphoma , endometrium adenocarcinoma endometrioid , kidney angiomyolipoma , kidney carcinoma , kidney oncocytoma , liver focal nodular hyperplasia , liver hepatocellular carcinoma , lymph node Hodgkin's disease , lymph node papillary carcinoma of thyroid , medullary carcinoma of thyroid origin , metastatic adenocarcinoma of stomach , neurofibroma , ovary thecoma fibroma , pancreas adenocarcinoma , pancreas microcystic adenoma , parathyroid gland adenoma , rectum adenocarcinoma , skin squamous cell carcinoma , spleen chronic myeloid leukemia , stomach gastrointestinal stromal tumor (GIST) , thyroid gland nodular hyperplasia , thyroid ...

Peptides and nanoparticles for intracellular delivery of molecules

The present invention pertains to peptides and peptide-containing complexes/nanoparticles that are useful for stabilizing and delivering cargo molecules such as nucleic acids.

Methods and compositions for generating an immune response by inducing cd40 and pattern recognition receptor adapters

Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible pattern recognition receptor adapter, or adapter fragment, and CD40 activity. Also provided are nucleic acid compositions comprising sequences coding for chimeric proteins that include an inducible CD40 peptide and an inducible pattern recognition receptor adapter or adapter fragment.

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES AND SCAFFOLDS THEREOF FOR USE IN IMMUNOTHERAPY AGAINST COLORECTAL CARCINOMA (CRC) 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. An expression vector expressing a nucleic acid encoding a peptide consisting of the amino acid sequence of KQFEGTVEI (SEQ ID NO: 138) or ALAAARVEL (SEQ ID NO: 17).2. A recombinant host cell comprising the peptide according to .3. A recombinant host cell comprising the nucleic acid according to .4. A recombinant host cell presenting HLA-A*02 on its surface comprising the expression vector according to claim 1 , wherein said host cell is optionally an antigen presenting cell.5. A method for producing a peptide consisting of the amino acid sequence of KQFEGTVEI (SEQ ID NO: 138) or ALAAARVEL (SEQ ID NO: 17) claim 3 , comprising culturing the host cell according to claim 3 , and isolating the peptide from the host cell or its culture medium.6. An in vitro method for producing activated T lymphocytes claim 3 , comprising contacting in vitro T cells with antigen loaded human HLA-A*0201 expressed on the surface of a suitable antigen-presenting cell or an artificial construct mimicking an antigen-presenting cell for a period of time sufficient to activate said T cells in an antigen specific manner claim 3 , wherein said antigen is a peptide consisting of the amino acid sequence of KQFEGTVEI (SEQ ID NO: 138) or ALAAARVEL (SEQ ID NO: 17).7. A method of treating a HLA-A* ...

CD33 SPECIFIC CHIMERIC ANTIGEN RECEPTORS

Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from a CD33 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders such as acute myeloid leukemia (AML), and relapsed or refractory AML. 113.-. (canceled)14. A vector comprising a backbone and a nucleic acid sequence encoding:(1) a truncated epidermal growth factor receptor comprising at least one of HER1t, HER1t-1 or a functional variant thereof; and (a) a CD33 antigen binding domain;', '(b) a stalk domain;', '(c) a transmembrane domain;', '(d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and', '(e) a CD3 zeta signaling domain., '(2) a chimeric antigen receptor (CAR), wherein the CAR comprises'}15. (canceled)16. The vector of claim 14 , wherein the vector is a lentivirus vector claim 14 , a retroviral vector claim 14 , or a non-viral vector.17. The vector of claim 14 , wherein the truncated epidermal growth factor receptor comprises a polypeptide having at least 90% claim 14 , 91% claim 14 , 92% claim 14 , 93% claim 14 , 94% claim 14 , 95% claim 14 , 96% claim 14 , 97% claim 14 , 98% claim 14 , 99% or 100% identity with the amino acid sequence of SEQ ID NO:32 or SEQ ID NO: 54.1823.-. (canceled)24. The vector of claim 14 , wherein the CD33 antigen binding domain comprises at least one of:(a) a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO:8 (hM195scFv);(b) a polypeptide having at least 900/%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99°/or 100% identity with the amino acid sequence of SEQ ID NOs:9 and 10 (M2H12);(c) a polypeptide having at least 900%, 91%, 92%, 93%, 94%, 95%, 96%, 97°/%, 98%, 99%0 or 100% identity with the amino acid sequence of SEQ ID NOs:11 and 12 (DRB2); and(d) a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% ...

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.

Novel generation of antigen-specific tcrs

The present invention contemplates methods for the generation of human antigen-specific T lymphocytes. The methods employ MHC class-II targeting signals fused to an antigen or fragment thereof to obtain MHC class presentation of RNA coded proteins. Accordingly, the present invention concerns expression vectors comprising MHC class-II targeting signal and at least one antigen or fragment thereof and its use for the in vitro generation of antigen-specific T lymphocytes. T cell clones and T cell receptors (TCRs) specific for tumor antigens or viral antigens are also described.

COMPOSITIONS AND METHODS FOR USE OF RECOMBINANT T CELL RECEPTORS FOR DIRECT RECOGNITION OF TUMOR ANTIGEN

Provided are compositions and methods for prophylaxis and/or therapy of a variety of cancers which express a NY-ESO-1 antigen. Included are recombinant T cell receptors (TCRs), polynucleotides encoding them, expression vectors that include the polynucleotides, and cells into which the polynucleotides have been introduced to produce modified cells, including CD4 T cells, CD8 T cells, natural killer T cells, γδ T cells, and progenitor cells, such as haematopoietic stem cells. The modified cells are capable of direct recognition of a cancer cell expressing a NY-ESO-1 antigen by human leukocyte antigen (HLA) class II-restricted binding of the TCR to the NY-ESO-1 antigen expressed by the cancer cell without presentation of the antigen by antigen presenting cells. In embodiments, the NY-ESO-1 antigen is displayed by the tumor cells. Also included is a method for prophylaxis and/or therapy of cancer by administering modified cells that express a recombinant TCR. Methods for making expression vectors and/or cells which express a recombinant TCR and identifying TCRs to make the expression vectors are also included. 1. A modified human hematopoietic stem cell comprising a recombinant polynucleotide encoding a T cell receptor (TCR) , wherein the recombinant polynucleotide encodes a TCR alpha chain having the sequence of SEQ ID NO:3 and a TCR beta chain having the sequence of SEQ ID NO:4 , or wherein the recombinant polynucleotide encodes a TCR alpha chain having the sequence of SEQ ID NO:11 and a TCR beta chain having the sequence of SEQ ID NO:12.2. The modified cell of claim 1 , comprising the recombinant polynucleotide that encodes the TCR alpha chain having the sequence of SEQ ID NO:3 and the TCR beta chain having the sequence of SEQ ID NO:4.3. The modified cell of claim 1 , comprising the recombinant polynucleotide that encodes the TCR alpha chain having the sequence SEQ ID NO:11 and the TCR beta chain having the sequence of SEQ ID NO:12.4. A method for prophylaxis and/or ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST VARIOUS TUMORS

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 eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells that aberrantly express a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1 , from SEQ ID NO: 3 to SEQ ID NO: 10 , SEQ ID NO: 12 , SEQ ID NO: 13 , from SEQ ID NO: 15 to SEQ ID NO: 23 , from SEQ ID NO: 26 to SEQ ID NO: 42 , from SEQ ID NO: 44 to SEQ ID NO: 83 , from SEQ ID NO: 85 to SEQ ID NO: 116 , from SEQ ID NO: 118 to SEQ ID NO: 156 , from SEQ ID NO: 158 to SEQ ID NO: 232 , from SEQ ID NO: 234 to SEQ ID NO: 242 , SEQ ID NO: 244 , from SEQ ID NO: 247 to SEQ ID NO: 252 , from SEQ ID NO: 254 to SEQ ID NO: 263 , and from SEQ ID NO: 265 to SEQ ID NO: 288;wherein said cancer is selected from the group consisting of hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), chronic lymphocytic leukemia (CLL), Merkel cell carcinoma (MCC), small cell lung cancer (SCLC), Non-Hodgkin ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST LUNG CANCER, INCLUDING NSCLC, SCLC 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 eliciting an immune response in a patient who has lung cancer , comprising administering to the patient a population of activated T cells that selectively recognize cells that present a peptide consisting of the amino acid sequence of SEIEQEIGSL (SEQ ID NO: 478).2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , wherein the activated T cells are expanded in vitro.6. The method of claim 1 , wherein the population of activated T cells are administered in the form of a composition.7. The method of claim 6 , wherein the composition further comprises an adjuvant.8. The method of claim 7 , wherein the adjuvant is selected from anti-CD40 antibody claim 7 , imiquimod claim 7 , resiquimod claim 7 , GM-CSF claim 7 , cyclophosphamide claim 7 , sunitinib claim 7 , bevacizumab claim 7 , interferon-alpha claim 7 , interferon-beta claim 7 , CpG oligonucleotides and derivatives claim 7 , poly-(I:C) and derivatives claim 7 , RNA claim 7 , sildenafil claim 7 , particulate formulations with poly(lactide ...

TRANSGENE GENETIC TAGS AND METHODS OF USE

The present invention provides genetic tags operably linked to transgenes. The expression of the genetic tag allows identification, detection, selection, and ablation of cells expressing the transgene and the genetic tag. In some alternatives the genetically modified host cell comprises a transgene comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain and a polynucleotide coding for a genetic tag. In some alternatives the genetically modified host cell comprises a transgene comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain and a polynucleotide coding for a genetic tag, and wherein the polypeptide further comprises a flexible linker comprising amino acids GGGSGGGS (SEQ ID NO:45). Pharmaceutical formulations produced by the method, and methods of using the same, are also described. 148.-. (canceled)49. A nucleic acid comprising a first polynucleotide encoding a fusion protein , wherein the fusion protein comprises:an extracellular domain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO:18;a spacer, wherein the spacer is selected from the group consisting of a CD28 hinge domain, an IgG4 hinge domain, and a polypeptide comprising the amino acid sequence of SEQ ID NO:45; anda transmembrane domain, wherein the transmembrane domain is linked to the extracellular domain via the spacer.50. The nucleic acid of claim 49 , wherein the spacer comprises the amino acid sequence of SEQ ID NO:45.51. The nucleic acid of claim 49 , wherein the spacer comprises the IgG4 hinge domain.52. The nucleic acid of claim 51 , wherein the ...

TREATMENT OF CANCER USING A CD123 CHIMERIC ANTIGEN RECEPTOR

The invention provides compositions and methods for treating diseases associated with expression of CD123. The invention also relates to chimeric antigen receptor (CAR) specific to CD123, vectors encoding the same, and recombinant cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CD123 binding domain. 1. An isolated nucleic acid molecule encoding a chimeric antigen receptor (CAR) , wherein the CAR comprises a humanized CD123 binding domain , a transmembrane domain , and an intracellular signaling domain , and wherein said CD123 binding domain comprises a heavy chain variable domain region comprising a heavy chain complementary determining region 1 (HC CDR1) , a heavy chain complementary determining region 2 (HC CDR2) , and a heavy chain complementary determining region 3 (HC CDR3) and light chain variable domain region comprising a light chain complementary determining region 1 (LC CDR1) , a light chain complementary determining region 2 (LC CDR2) , and a light chain complementary determining region 3 (LC CDR3) , wherein:(a) the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and LC CDR3 sequences comprise the amino sequences of SEQ ID NO: 490, 495, 500, 505, 510, and 515, respectively;(b) the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and LC CDR3 sequences comprise the amino sequences of SEQ ID NO: 520, 525, 530, 535, 540, and 555, respectively;(c) the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and LC CDR3 sequences comprise the amino sequences of SEQ ID NO: 361, 389, 417, 445, 473, and 47, respectively.24.-. (canceled)5. The isolated nucleic acid molecule of claim 1 , which encodes a CAR comprising:(i) the amino acid sequence of the light chain variable region of SEQ ID NO: 302-333;(ii) an amino acid sequence having at least one, two or three modifications but not more than 30, 20 or 10 modifications of the amino acid sequence of the light chain variable region of SEQ ID ...

CELL FOR USE IN IMMUNOTHERAPY WHICH CONTAINS MODIFIED NUCLEIC ACID CONSTRUCT ENCODING WILMS TUMOR GENE PRODUCT OR FRAGMENT THEREOF, METHOD FOR PRODUCING SAID CELL, AND SAID NUCLEIC ACID CONSTRUCT

A cell of the present invention contains a nucleic acid construct encoding a WT1 gene product or a fragment of the WT1 gene product. The nucleic acid construct contains (i) a region encoding a desired fragment of the WT1 gene product and (ii) only AUG as a functional start codon. The present invention can provide a cell into which the nucleic acid construct is introduced so that an expression level of a WT1 gene product or a fragment of the WT1 gene product is remarkably enhanced. 1. A cell for immunotherapy , comprising:a nucleic acid construct encoding a Wilms tumor gene product or a fragment of the Wilms tumor gene product,the nucleic acid construct including (i) a region encoding a fragment of the Wilms tumor gene product, the fragment being indicated by positions 194 to 493 of SEQ ID NO: 1 or by positions corresponding to the positions 194 to 493 of a sequence corresponding to SEQ ID NO: 1 and (ii) only one AUG as a functional start codon, connected to a 5′ terminal side of the region via 3m (m is 0 or a positive integer) bases intervening between the 5′ terminal side of the region and the AUG as the functional start codon.2. The cell as set forth in claim 1 , wherein:as the region encoding the fragment of the Wilms tumor gene product, the nucleic acid construct includes a region encoding a fragment of the Wilms tumor gene product, the fragment being indicated by positions 69 to 517 of SEQ ID NO: 1 or by positions corresponding to the positions 69 to 517 of a sequence corresponding to SEQ ID NO: 1; andthe nucleic acid construct is such that all of CUG at positions 191 to 193 are deleted or C of CUG at positions 191 to 193 is substituted with A in the sequence indicated by SEQ ID NO: 2.3. The cell as set forth in claim 1 , wherein a production amount of proteins directly translated from the nucleic acid construct is 25 times or more as large as that of proteins directly translated from RNA including a coding region indicated by positions 191 to 1741 of SEQ ID NO ...

USE OF CHIMERIC ANTIGEN RECEPTOR T CELLS AND NK CELL INHIBITORS FOR TREATING CANCER

Methods for improving a clinical outcome in a subject comprising administering to a subject in need of the treatment a population of genetically engineered immune cells (e.g., T cells), which express a chimeric antigen receptor (CAR) and a natural killer (NK) cell inhibitor (e.g., daratumumab). The genetically engineered immune cells may comprise a disrupted TRAC gene, a disrupted B2M gene, or both. The disclosure also features compositions for use in the methods. 1. A method for treating cancer , the method comprising administering to a human cancer patient:(a) an effective amount of an NK cell inhibitor; and(b) an effective amount of a population of engineered human T cells expressing a CAR (CAR T cells), wherein the engineered human CAR T cells comprise disrupted MHC class I, and wherein the CAR comprises an ectodomain that comprises an antigen-binding fragment, which binds a tumor antigen.2. The method of claim 1 , wherein the engineered human CAR T cells comprise a disrupted beta-2-microglobulin (β2M) gene.3. The method of claim 1 , wherein the engineered human CAR T cells comprise:(i) a disrupted T cell receptor alpha chain constant region (TRAC) gene;(ii) a disrupted β2M gene; and(iii) a nucleic acid encoding the CAR.4. The method of claim 3 , wherein the nucleic acid encoding the CAR is inserted in the disrupted TRAC gene.5. The method of claim 1 , wherein the tumor antigen is CD19 claim 1 , CD33 claim 1 , CD70 or BCMA.6. The method of claim 1 , wherein the NK cell inhibitor is an antibody that specifically binds CD38.7. The method of claim 6 , wherein the antibody is daratumumab claim 6 , SAR650984 claim 6 , or MOR202 claim 6 , or an antigen-binding fragment thereof.8. The method of claim 1 , wherein the NK cell inhibitor is administered prior to administration of the population of engineered human CAR T cells.9. The method of claim 1 , wherein the method further comprises a pre-conditioning regimen prior to administration of the population of engineered ...

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING GASTROINTESTINAL AND GASTRIC CANCER

A pharmaceutical composition contains an antibody or a fragment thereof specific for COL6A3 for the treatment of a cancer. A method of treating a cancer includes administering to a subject in need thereof the pharmaceutical composition. A kit includes a container that contains the pharmaceutical composition. A method of producing an antibody or a fragment thereof against a peptide or a MHC/peptide complex. A method for detecting a diseased tissue includes administering to a subject in need thereof an antibody or a fragment thereof conjugated to a radioisotope and detecting a signal from the radioisotope in the subject. A method for treating a diseased tissue includes administering to a subject in need thereof an antibody or a fragment thereof conjugated to a toxin. 1. A peptide consisting of the amino acid sequence LYQILQGIVF (SEQ ID NO: 1) in the form of a pharmaceutically acceptable salt.2. The peptide of claim 1 , wherein said peptide has the ability to bind to an MHC class-I molecule claim 1 , and wherein said peptide claim 1 , when bound to said MHC claim 1 , is capable of being recognized by CD8 T cells.3. The peptide of claim 1 , wherein the pharmaceutically acceptable salt is chloride salt.4. The peptide of claim 1 , wherein the pharmaceutically acceptable salt is acetate salt.5. A composition comprising the peptide of claim 1 , wherein the composition comprises an adjuvant and a pharmaceutically acceptable carrier.6. The composition of claim 5 , wherein the peptide is in the form of a chloride salt.7. The composition of claim 5 , wherein the peptide is in the form of an acetate salt.8. The composition of wherein the adjuvant is selected from the group consisting of anti-CD40 antibody claim 5 , imiquimod claim 5 , resiquimod claim 5 , GM-CSF claim 5 , cyclophosphamide claim 5 , sunitinib claim 5 , bevacizumab claim 5 , interferon-alpha claim 5 , interferon-beta claim 5 , CpG oligonucleotides and derivatives claim 5 , poly-(I:C) and derivatives claim 5 , RNA ...

IMMUNOSUPPRESSIVE ANTIGEN-SPECIFIC CHIMERIC ANTIGEN RECEPTOR TREG CELLS FOR PREVENTION AND/OR TREATMENT OF AUTOIMMUNE AND ALLOIMMUNE DISORDERS

Described herein are immunoresponsive cells which are useful for their preventive and therapeutic potential against autoimmune diseases and rejections of solid organ transplants. 1. An immunoresponses cell comprising:a chimeric antigen receptor (CAR) that binds to glutamic acid decarboxylase 65 kDA (GAD65) in the cell;the CAR comprising:a) an intracellular signaling domain of a CD3ξ polypeptide and an intracellular signaling domain of CD28 hinge-transmembrane-intracellular region, andb) an extracellular polypeptide recognizing: at least a part of an amino acid sequence selected from the amino acids having SEQ ID Nos: 1-6; or, at least one complete amino acid sequence selected from the amino acids having SEQ ID Nos: 1-6.2. The immunoresponsive cell of claim 1 , wherein the immunoresponsive cell is selected from the group consisting of: T cells claim 1 , cytotoxic T cells claim 1 , regulatory T cells claim 1 , and combinations thereof.3. The immunoresponsive cell of claim 1 , wherein the immunoresponsive cell comprises a pancreatic beta cell-specific chimeric antigen receptor (CAR) regulatory T cell (Treg) that expresses at least one extracellular polypeptide and is capable of affecting Teff cells.4. The immunosuppressive cell of claim 1 , wherein the extracellular polypeptide is a GAD65 MAb antigen binding domain which recognizes: at least a part of an amino acid sequence selected from the amino acids having SEQ ID Nos: 1-6; or claim 1 , at least one complete amino acid sequence selected from the amino acids having SEQ ID Nos: 1-6.5. A pharmaceutical composition comprising an effective amount of an immunoresponsive cell of and a pharmaceutically acceptable excipient.6. The pharmaceutical composition of claim 5 , wherein the immunoresponsive cell is a T cell.7. (canceled)8. A method of lengthening survival of a subject having type 1 diabetes (T1D) claim 5 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the subject an ...

Vaccination with microvesicles derived from tumour cells for cancer treatment

The present invention relates to microvesicles derived from natural tumor cells and tumor cells produced in vitro under a stress stimulus, such as radiation, which can be used in an effective manner as a therapeutic vaccine for cancer. The invention also relates to a therapeutic vaccine formulation containing the microvesicles, processes for the preparation and medical use thereof as a therapeutic vaccine to stimulate the antitumor immune system and treat cancer.

Pharmaceutical composition for use in the treatment of pancreatic cancer

The present invention relates to a method for the treatment of pancreatic cancer comprising administering to a patient in need thereof a CD40 agonist in combination with dendritic cells loaded with a lysate of mesothelioma cells. A further aspect of the present invention relates to dendritic cells loaded with a lysate of mesothelioma cells for use in the treatment of pancreatic cancer. A last aspect of the present invention relates to a pharmaceutical composition comprising such loaded dendritic cells.