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

НОВАЯ СУБПОПУЛЯЦИЯ CD8+CD45RClow КЛЕТОК TREG И ЕЕ ПРИМЕНЕНИЯ

Настоящее изобретение относится к клеточной биологии, в частности к выделенной популяции CD8+CD45RClow клеток Treg, секретирующих IFNγ+IL-10+IL-34+, фармацевтической композиции для предотвращения или лечения отторжения трансплантата, РТПХ, хронических воспалительных заболеваний, аутоиммунных заболеваний, нежелательного иммунного ответа против терапевтических белков или аллергий, а также способам детектирования, выделения и размножения CD8+CD45RClow клеток Treg, секретирующих IFNγ+IL-10+IL-34+, применению указанной популяции для предотвращения или лечения и способу определения риска указанных заболеваний. Настоящее изобретение раскрывает новую субпопуляцию CD8+CD45RClow клеток Treg. 7 н. и 6 з.п. ф-лы, 15 ил., 1 пр.

Method of inducing memory B cell development and terminal differentiation

A method for preparing lymphohaematopoietic progenitor cells

Transcription factor mediated programming towards megakaryocytes

A method of preparing an undifferentiated cell

A method of preparing an undifferentiated cell.

A method of preparing an undifferential cell is described. The method comprises contacting a more committed cell with an agent that causes the more committed cell to retrodifferentiate into an uundifferentiated cell.

A method of preparing an undifferentiated cell

A method of preparing an undifferentiated cell

ANTIGEN PRESENTING SYSTEM AND ACTIVATION OF T-CELLS

Artificial antigen presenting cells including HLA-E and HLA-G molecules and methods of use

The present disclosure relates to artificial antigen presenting cells (aAPCs), in particular engineered erythroid cells and enucleated cells ( ...

TUMOR-INFILTRATING LYMPHOCYTES FOR ADOPTIVE CELL THERAPY

Disclosed are compositions and methods for ex vivo expansion of tumor infiltrating lymphocytes for use in adoptive cell therapy (ACT). Also disclosed are compositions and method for identifying an agent for ex vivo expansion of tumor infiltrating lymphocytes for use in ACT. Also disclosed are methods for treating cancer using tumor-infiltrating lymphocytes expanded by the disclosed methods.

Methods and compositions for natural killer cells

The application provides new compositions and methods for stimulating the production of natural killer (NK) cells in a subject. NK cells can be selectively expanded with a combination of stimulating ligands. Methods and compositions for the administration of stimulatory ligands modified to self-insert into tumor cells, thereby stimulating an increase in the number of NK cells in proximity to a tumor, are also described.

Method

The invention concerns a method of generating an immune response in a subject, comprising administering to the subject an antigenic molecule, a photosensitizing agent, a checkpoint inhibitor, and irradiating said subject with light of a wavelength effective to activate the photosensitizing agent to generate an immune response. Preferably the method is a method of vaccination. The invention also provides related methods, compositions, cells, uses, products and kits.

Composition for differentiation induction of adipocyte containing stem cell-derived exosome, regeneration of adipose tissue, and skin whitening or wrinkle improvement

The present invention relates to a pharmaceutical composition for adipocyte differentiation induction and/or adipose tissue regeneration comprising, as an active ingredient, an exosome extracted from a stem cell which is differentiating into an adipocyte. The exosome is excellent in expression rate of bioactive factors influencing the differentiation into an adipocyte and has the effect of differentiating a stem cell into an adipocyte. Accordingly, the present invention can be applied to differentiation inducing agents of a stem cell, injections for tissue regeneration, fillers for cosmetic purposes, preparations for tissue engineering, etc. The invention also relates to a cosmetic composition for skin whitening, wrinkle improvement and regeneration, containing an exosome extracted from a stem cell as an active ingredient. Since the exosome contains genes, proteins, growth factors etc. associated with the proliferation, differentiation, and regeneration of stem cells; is a purified component ...

Production method for retinal tissue

The present invention provides a production method for retinal cells or retinal tissue, the method including steps (1)-(3): (1) a first step for culturing human pluripotent stem cells in the absence of feeder cells in a culture medium that includes a non-differentiation maintenance factor; (2) a second step for culturing the pluripotent stem cells obtained in the first step in suspension in the presence of a sonic hedgehog signal transduction pathway activator so as to form an aggregate of cells; and (3) a third step for culturing the aggregate obtained in the second step in suspension in the presence of a BMP signal transduction pathway activator so as to obtain an aggregate that includes retinal cells or retinal tissue.

METHOD FOR ISOLATING AND PROLIFERATING SELF-TUMOR ANTIGEN SPECIFIC CD8+ T CELLS

Provided is a method for isolating and proliferating autologous cancer antigen-specific CD8*T cells, and more particularly, a method for selecting an 5 epitope recognized by CD8' T cells from autologous cancer antigens present in blood of individual cancer patients; and isolating autologous cancer antigen-specific CD8' T cells by using a peptide of the selected epitope, and a method of massively proliferating CD8' T cells by using the method. According to the present invention, it is possible to isolate autologous cancer antigen-specific CD8' T cells by using the 10 peptide of the CD8 T cell epitope of the autologous cancer antigen present in blood of individual cancer patients instead of a heterologous antigen. Therefore, by using T cells recognizing the autologous cancer antigen, it is possible to effectively select and eliminate cancer cells derived from the cancer patient's own cells. Thus, T cells can be applied to treatment and alleviation of cancer diseases without side effects.

Medium, methods, cells and secreted factors for stem cell culture and therapy

MEDIUM, METHODS, CELLS AND SECRETED FACTORS FOR STEM CELL CULTURE AND THERAPY Described herein are methods and culture medium, useful for inducing polarization in multipotent stem cells. Additionally, described herein are multipotent cells produced by the methods and culture medium of this disclosure that are useful therapeutic agents. Also described herein are extracellular vesicles and factors secreted by multipotent cells that are produced by the methods and culture medium of this disclosure that are useful as therapeutic agents.

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

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

REGULATORY T CELL EPITOPES, COMPOSITIONS AND USES THEREOF

The invention is directed to T cell epitopes wherein said epitopes compri ses a peptide or polypeptide chain comprising at least a portion of an immun oglobulin constant or variable region. The invention also relates to methods of using and methods of making the epitopes of the invention.

PROCESS FOR PRODUCING GENETICALLY ENGINEERED T CELLS

The present disclosure provides cell populations enriched for CD57 negative T cells, or depleted for CD57 positive cells, and methods for stimulating, cultivating, expanding, and/or genetically engineering cell populations enriched for CD57- T cells or depleted for CD57+ T cells. Also included are methods for generating, isolating, enriching, or selecting CD57- T cells or depleting CD57+ cells, such as by negative selection.

PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST NON-SMALL CELL LUNG 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.

A METHOD OF PREPARING AN UNDIFFERENTIATED CELL

A method of preparing an undifferentiated cell is described. The method comprises contacting a more committed cell with an agent that causes the more committed cell to retrodifferentiate into an undifferentiated cell.

COMPOSITIONS FOR THE PREPARATION OF MATURE DENDRITIC CELLS

The invention relates to a method for in vitro maturation of at least one immature dendritic cell, comprising stimulating said immature dendritic cell with TNF.alpha., IL- l.beta., IFN.gamma., a TLR7/8 agonist and prostaglandin E2 (PG). Furthermore, the invention relates to a composition comprising said factors as well as to mature dendritic cells produced by the method of the invention.

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING NEURONAL AND BRAIN TUMORS

... ²The present invention relates to peptides, nucleic acids and cells for use in ²immunotherapeutic ²methods. In particular, the present invention relates to the immunotherapy of ²cancer. The present ²invention furthermore relates to tumor-associated cytotoxic T cell (CTL) ²peptide epitopes, alone ²or in combination with other tumor-associated peptides that serve as active ²pharmaceutical ²ingredients of vaccine compositions that stimulate anti-tumor immune ²responses. The present ²invention relates to 30 peptide sequences and their variants derived from HLA ²class I and class II ²molecules of human tumor cells that can be used in vaccine compositions for ²eliciting anti-tumor ²immune responses.² ...

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING NEURONAL AND BRAIN TUMORS

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 30 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.

METHODS OF PRODUCING AND USING REGULATORY B-CELLS

The invention is directed to a method of preparing B-cells that produce interleukin-10 (IL-10), or IL-10 per se, which comprises contacting one or more B-cells ex vivo with an isolated interleukin-35 (IL-35) protein, and culturing the one or more B-cells under conditions to provide one or more B-cells that produce IL-10. The invention also is directed to a method of suppressing the proliferation of lymphocytes in vitro or in vivo by contacting lymphocytes with an isolated IL-35 protein. The invention further is directed to a method of suppressing autoimmunity in a mammal by administering to the mammal an IL-35 protein or IL-10-producing B-cells.

Device and method for the preparation of undifferentiated cells.

L'invention concerne un dispositif pour la formation et/ou l'augmentation du nombre relatif de cellules indifférenciées dans une population cellulaire comprenant des cellules engagées. Le dispositif comprend un moyen pour mettre en contact une cellule plus engagée avec un agent qui provoque la rétrodifférenciation de la cellule plus engagée en une cellule indifférenciée. Application: procédé pour la préparation d'une cellule indifférenciée.

Device and method for the preparation of undifferentiated cells.

COMPOSITION OPUKhOLEASSOTsIIROVANNYKh PEPTIDES AND RELATED ANTI-CANCER VACCINE FOR TREATMENT OF GLIOBLASTOMA (GBM) AND OTHER TYPES OF CANCER

NEW PEPTIDES AND COMBINATIONS OF PEPTIDES FOR USE IN IMMUNOTHERAPY OVARY CANCER AND OTHER TYPES OF CANCER

NEW PEPTIDES AND COMBINATIONS OF PEPTIDES FOR USE IN IMMUNOTHERAPY NHL AND OTHER TYPES OF CANCER

NEW PEPTIDES AND COMBINATIONS OF PEPTIDES FOR USE IN IMMUNOTHERAPY OF LUNG CANCER, INCLUDING NEMELKO CELLULAR LUNG CANCER (NMRL), SMALL CELL LUNG CANCER (MRL) AND OTHER TYPES OF CANCER

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

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

METHODS OF MATURING PLASMACYTOID DENDRITIC CELLS USING IMMUNE RESPONSE MODIFIER MOLECULES

The present invention relates to methods of maturing plasmacytoid dendritic cells using immune response modifier molecules. The present invention also relates to methods of detecting biological activities of matured plasmacytoid dendritic cells and methods of using mature plasmacytoid dendritic cells for therapeutic or prophylactic purposes.

METHODS FOR IMPROVING THE EFFICACY AND EXPANSION OF IMMUNE CELLS

The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), compositions and reaction mixtures comprising the same, and methods of treatment using the same.

PRODUCTION METHOD FOR RETINAL TISSUE

The present invention provides a method for producing retinal cells or a retinal tissue, comprising the following steps (1)-(3): (1) a first step of culturing human pluripotent stem cells in the absence of feeder cells and in a medium comprising a factor for maintaining undifferentiated state, (2) a second step of culturing the pluripotent stem cells obtained in the first step in suspension in the presence of a Sonic hedgehog signal transduction pathway activating substance to form a cell aggregate, and (3) a third step of culturing the aggregate obtained in the second step in suspension in the presence of a 1) a BMP signal transduction pathway activating substance to obtain an aggregate containing retinal cells or a retinal tissue.

Pluripotent cell lines and methods of use thereof

Methods of generating cell lines with a sequence variation or copy number variation of a gene of interest, methods of use thereof, and cell lines with a sequence variation or copy number variation of a gene of interest are provided.

Methods Of Isolating Distinct Pancreatic Cell Types

Methods of isolating distinct specific cell types within mixed populations of cells. Methods of isolating specific cell types among pancreatic cells, particularly from human islets of Langerhans. Markers and combinations thereof for use in methods of isolating insulin producing islet beta cells for treatment of diabetes.

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

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

ГАНГЛИОЗИДЫ ДЛЯ СТАНДАРТИЗАЦИИ И ПОВЫШЕНИЯ ЧУВСТВИТЕЛЬНОСТИ КЛЕТОК К НЕЙРОТОКСИНАМ БОТУЛИЗМА В ТЕСТ-СИСТЕМАХ IN VITRO

ДИФФЕРЕНЦИРОВКА ЭМБРИОНАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК ЧЕЛОВЕКА В ПАНКРЕАТИЧЕСКИЕ ЭНДОКРИННЫЕ КЛЕТКИ

Peptides and combination of peptides for use in immunotherapy against cancers

PROCEDURE FOR THE PRODUCTION OF ANTIGEN-SPECIFIC TR1REGUALTORI LYMPHOZYTEN

USE OF GLYKOPROTEIN ACA ANTIBODY FOR PRODUCTION OR PRESERVATION OF PLURIPOTENTEN NICHTEMBRYONALEN MAIN CELLS

Process for producing genetically engineered T cells

The present disclosure provides cell populations enriched for CD57 negative T cells, or depleted for CD57 positive cells, and methods for stimulating, cultivating, expanding, and/or genetically engineering cell populations enriched for CD57- T cells or depleted for CD57+ T cells. Also included are methods for generating, isolating, enriching, or selecting CD57- T cells or depleting CD57+ cells, such as by negative selection.

Medium, methods, cells and secreted factors for stem cell culture and therapy

Described herein are methods and culture medium, useful for inducing polarization in multipotent stem cells. Additionally, described herein are multipotent cells produced by the methods and culture medium of this disclosure that are useful therapeutic agents. Also described herein are extracellular vesicles and factors secreted by multipotent cells that are produced by the methods and culture medium of this disclosure that are useful as therapeutic agents.

Novel peptides and combination of peptides for use in immunotherapy against lung cancer, including NSCLC 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.

NOVEL PEPTIDES, COMBINATION OF PEPTIDES AND SCAFFOLDS FOR USE IN IMMUNOTHERAPEUTIC TREATMENT OF VARIOUS CANCERS

Abstract The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immu notherapy 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 composi tions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

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

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

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

NOVEL PEPTIDES, COMBINATION OF PEPTIDES AND SCAFFOLDS FOR USE IN IMMUNOTHERAPEUTIC TREATMENT OF VARIOUS CANCERS

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

Macrophages eat cancer cells using their own calreticulin as a guide

Therapeutic and diagnostic methods are provided, which methods relate to the induction of expression of calreticulin on phagocytic cells. Specifically, the methods relate to macrophage-mediated programmed cell removal (PrCR), the methods comprising increasing PrCR by contacting a phagocytic cell with a toll-like receptor (TLR) agonist; or down-regulating PrCR by contacting a phagocytic cell with an inhibitor of Bruton's tyrosine kinase (BTK). In some embodiments, an activator of TLR signaling or a BTK agonist is provided in combination with CD47 blockade.

METHOD FOR OBTAINING ANTIGEN-SPECIFIC TR1 REGULATORY LYMPHOCYTES

L'invention concerne un procédé de préparation de lymphocytes régulateurs Tr1 spécifiques d'antigène, utilisant des cellules présentatrices de l'antigène artificielles, exprimant une molécule du système HLA de classe II et une molécule de LFA-3 humain et n'exprimant aucune des molécules de co-stimulation B7-1, B7-2, B7-H1, CD40, CD23 ou ICAM-1.

ALS TREATMENT USING INDUCED REGULATORY T (ITREG) CELLS

The present disclosure provides methods for treating ALS using pentostatin and cyclophosphamide treatment followed by TREG and/or TREG/Th2 hybrid cells from dedifferentiated T cells. The present disclosure further provides methods for producing TREG and TREG/Th2 hybrid cells from de-differentiated T cells, said TREG and TREG/Th2 hybrid cells, populations thereof and compositions thereof. Methods for producing de-differentiated T cells, said de-differentiated T cells, populations thereof and compositions thereof are also provided.

METHODS OF T CELL EXPANSION AND ACTIVATION

The present disclosure relates to methods, cells, and compositions for preparing T cell populations and compositions for adoptive cell therapy. In particular, provided herein are methods for efficiently expanding and activating T cell populations for genetic engineering and adoptive T cell immunotherapies. Also provided are cells and compositions produced by the methods and methods of their use.

COMPOSITION OF TUMOR-ASSOCIATED PEPTIDES AND RELATED ANTI-CANCER VACCINE FOR THE TREATMENT OF GLIOBLASTOMA (GBM) AND OTHER CANCERS

The present invention relates to immunotherapeutic peptides and their use in immunotherapy, in particular the immunotherapy of cancer. The present invention discloses tumor-associated T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor immune responses. In particular, the composition of the peptides of the present invention can be used in vaccine compositions for eliciting anti-tumor immune responses against gliomas.

COMPOSITION OF TUMOR-ASSOCIATED PEPTIDES AND RELATED ANTI-CANCER VACCINE FOR THE TREATMENT OF GLIOBLASTOMA (GBM) AND OTHER CANCERS

The present invention relates to immunotherapeutic peptides and their use in immunotherapy, in particular the immunotherapy of cancer. The present invention discloses tumor-associated T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor immune responses. In particular, the composition of the peptides of the present invention can be used in vaccine compositions for eliciting anti-tumor immune responses against gliomas.

METHODS OF PRODUCING AND USING REGULATORY B-CELLS

The invention is directed to a method of preparing B-cells that produce interleukin-10 (IL-10), or IL-10 per se, which comprises contacting one or more B-cells ex vivo with an isolated interleukin-35 (IL-35) protein, and culturing the one or more B-cells under conditions to provide one or more B-cells that produce IL-10. The invention also is directed to a method of suppressing the proliferation of lymphocytes in vitro or in vivo by contacting lymphocytes with an isolated IL-35 protein. The invention further is directed to a method of suppressing autoimmunity in a mammal by administering to the mammal an IL-35 protein or IL-10-producing B-cells.

TUMOR-INFILTRATING LYMPHOCYTES FOR ADOPTIVE CELL THERAPY

Disclosed are compositions and methods for ex vivo expansion of tumorinfiltrating lymphocytes for use in adoptive cell therapy (ACT). Also disclosed are compositions and method for identifying an agent for ex vivo expansion of tumorinfiltrating lymphocytes for use in ACT. Also disclosed are methods for treating cancer using tumor-infiltrating lymphocytes expanded by the disclosed methods.

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING NEURONAL AND BRAIN TUMORS

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 30 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.

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING NEURONAL AND BRAIN TUMORS

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 30 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.

ATTACHMENT ENHANCED 293 CELLS

Attachment enhanced human embryonic kidney cells, 293, are provided. These cells have been modified to contain a selected mammalian scavenger gene, which has been found to improve the ability of the se cells to attach in culture. The improved cells of the invention are useful in assays in which the unmodified 293 cells could be used.

PEPTIDES FOR IMMUNOTHERAPY OF TUMORS, INCLUDING NEURONAL TUMORS AND BRAIN TUMORS

IMMUNOSKONSTRUIROVANNYE PLURIPOTENT STEM CELLS

NEW PEPTIDES AND COMBINATION PEPTIDES AND THEIR FRAMES FOR APPLICATION IN IMMUNOTHERAPY OF COLORECTAL CARCINOMA (CBC) AND OTHER TYPES OF CANCER

NEW PEPTIDES AND COMBINATIONS OF PEPTIDES FOR USE IN IMMUNOTHERAPY OVARY CANCER AND OTHER TYPES OF CANCER

NEW PEPTIDES AND COMBINATIONS OF PEPTIDES FOR USE IN IMMUNOTHERAPY OVARY CANCER AND OTHER TYPES OF CANCER

PENETRATING IN TUMOR LYMPHOCYTES FOR ADOPTIVNOI CELLULAR THERAPY

PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY NEMELKO CELL LUNG CANCER AND OTHER TYPES OF CANCER

Therapeutic applications of activation of human antigen-presenting cells through dectin-1

The present invention includes compositions and methods for binding Dectin-1 on immune cells with anti-Dectin-1-specific antibodies or fragment thereof capable of activating the immune cells.

Through DECTIN-1 activate human therapeutic uses of antigen presenting cells

Preparation of antigen-specific Tr1 regulatory lymphocytes, useful for treating inflammatory and autoimmune diseases, uses antigen-presenting cells that express HLA and LFA-3

L'invention concerne un procédé de préparation de lymphocytes régulateurs Tr1 spécifiques d'antigène, utilisant des cellules présentatrices de l'antigène artificielles, exprimant une molécule du système HLA de classe II et une molécule de LFA-3 humain et n'exprimant aucune des molécules de co-stimulation B7-1, B7-2, B7-H1, CD40, CD23 ou ICAM-1.

Method for culturing 3D lung cancer organoid and preparing patient-derived xenograft model using thereof

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

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES AND SCAFFOLDS THEREOF FOR USE IN IMMUNOTHERAPY AGAINST COLORECTAL CARCINOMA (CRC) AND OTHER CANCERS

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING NEURONAL AND BRAIN TUMORS

Cosmetic Composition Containing Exosomes Extracted from Stem Cell for Skin Whitening, Antiwrinkle or Regeneration

A cosmetic composition for skin whitening, wrinkle improvement or skin regeneration includes, as an active ingredient, exosomes derived from stem cells comprising proliferating stem cells.

Methods for producing proliferating muscle cells

The present invention is related to compositions and methods for expanding cell populations suitable for use as cardiac or skeletal muscle grafts. In particular, the present invention provides methods for regulation of cell cycle withdrawal and myoblast fusion during myogenesis.

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

PLURIPOTENT CELL LINES AND METHODS OF USE THEREOF

Methods of generating cell lines with a sequence variation or copy number variation of a gene of interest, methods of use thereof, and cell lines with a sequence variation or copy number variation of a gene of interest are provided.

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.

NOVEL PEPTIDES, COMBINATION OF PEPTIDES AND SCAFFOLDS FOR USE IN IMMUNOTHERAPEUTIC TREATMENT OF VARIOUS 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 for treating a patient who has cancer , comprising administering to the patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of SEQ ID NO: 236 , 1-235 , or 237-417 ,wherein the peptide is in a complex with an MHC molecule,wherein said cancer is selected from the group consisting of glioblastoma, breast cancer, colorectal cancer, renal cell carcinoma, chronic lymphocytic leukemia, hepatocellular carcinoma, non-small cell lung cancer, small cell lung cancer, Non-Hodgkin lymphoma, acute myeloid leukemia, ovarian cancer, pancreatic cancer, prostate cancer, esophageal cancer including cancer of the gastric-esophageal junction, gallbladder cancer and cholangiocarcinoma, melanoma, gastric cancer, testis cancer, urinary bladder cancer, head-and neck squamous cell carcinoma, and uterine 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 activated T cells are produced by contacting T cells with the peptide loaded human class I or II MHC molecules expressed on the surface of an antigen-presenting cell for a period of time sufficient to ...

PEPTIDES AND T CELLS FOR USE IN IMMUNOTHERAPEUTIC TREATMENT OF VARIOUS 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.

Peptides and combination of peptides for use in immunotherapy against 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.

USE OF THE ACA GLYCOPROTEIN FOR OBTAINING/MAINTAINING PLURIPOTENT NON-EMBRYONIC STEM CELLS

ANTIGEN PRESENTING SYSTEM AND METHOD FOR ACTIVATING T-CELL

PROBLEM TO BE SOLVED: To obtain a synthetic antigen presenting matrix, to provide a method for producing the same and a use thereof. SOLUTION: The synthetic antigen-presenting matrix comprises a non-cellular substrate, an extracellular part of MHC molecule that can be bonded to a selected peptide and operably linked to the substrate and an assisting molecule operably linked to the substrate so that the extracellular part of MHC and the assisting molecule exist in sufficient numbers to activate the group of T lymphocytes to the peptide when the peptide is bonded to the extracellular part of MHC molecules. The cells are transfected to produce MHC antigen-presenting molecules and assisting molecules such as co-stimulatory molecules. The matrix and the cells are used to activate CD8+T-cells to produce cytokines and become cytotoxic. COPYRIGHT: (C)2007,JPO&INPIT ...

СПОСОБ ПОЛУЧЕНИЯ НЕДИФФЕРЕНЦИРОВАННОЙ КЛЕТКИ

Изобретение относится к медицине, в частности клеточной иммунологии. Сущность изобретения состоит в том, что в клеточной популяции (в культуре) повышают число СD 34+ клеток за счет взаимодействия клеточной популяции (например, гемопоэтических клеток) с антителом, например СР3/43, при этом антитело может быть использовано в сочетании с алкилирующим агентом, например циклофосфамидом. Техническим результатом изобретения является расширение арсенала средств для лечения заболеваний иммунной системы. 19 з. п. ф-лы, 20 табл. , 6 ил.

НОВАЯ СУБПОПУЛЯЦИЯ CD8+CD45RClow КЛЕТОК TREG И ЕЕ ПРИМЕНЕНИЯ

Настоящее изобретение относится к клеточной биологии, в частности к выделенной популяции CD8+CD45RClow клеток Treg, секретирующих IFNγ+IL-10+IL-34+, фармацевтической композиции для предотвращения или лечения отторжения трансплантата, РТПХ, хронических воспалительных заболеваний, аутоиммунных заболеваний, нежелательного иммунного ответа против терапевтических белков или аллергий, а также способам детектирования, выделения и размножения CD8+CD45RClow клеток Treg, секретирующих IFNγ+IL-10+IL-34+, применению указанной популяции для предотвращения или лечения и способу определения риска указанных заболеваний. Настоящее изобретение раскрывает новую субпопуляцию CD8+CD45RClow клеток Treg. 7 н. и 6 з.п. ф-лы, 15 ил., 1 пр.

КОМПОЗИЦИЯ, ВКЛЮЧАЮЩАЯ ЭКЗОСОМУ, ПОЛУЧЕННУЮ ИЗ СТВОЛОВЫХ КЛЕТОК, ДЛЯ ИНДУКЦИИ АДИПОГЕННОЙ ДИФФЕРЕНЦИРОВКИ, РЕГЕНЕРАЦИИ ЖИРОВОЙ ТКАНИ, ОТБЕЛИВАНИЯ КОЖИ ИЛИ КОРРЕКЦИИ МОРЩИН

Группа изобретений относится к биотехнологии, а именно к композиции для индукции дифференцировки стволовых клеток в адипоциты. Композиция для индукции дифференцировки стволовых клеток в адипоциты для регенерации жировых тканей содержит в качестве ингредиента экзосомы, полученные из стволовых клеток, полученных из жировой ткани и дифференцирующихся в адипоциты, где экзосомы характеризуются тем, что содержат макрофагальный колониестимулирующий фактор (MCSF), фактор некроза опухоли-α (TNF-α), лептин, инсулин, ангиопоэтин-1 (ANGPT1) и адипонектин с молекулярной массой 30 кДа (Acrp30). Группа изобретений относится также к инъекционной форме препарата, содержащей указанную композицию. Использование данной группы изобретений позволяет применять данную композицию в качестве агентов, индуцирующих дифференцировку стволовых клеток, инъекционных форм препаратов для регенерации тканей путем экспрессии экзосомами биоактивных факторов, оказывающих воздействие на дифференцировку в адипоциты. 2 н. и 4 з.п ...

ДИФФЕРЕНЦИРОВКА ЭМБРИОНАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК ЧЕЛОВЕКА В ПАНКРЕАТИЧЕСКИЕ ЭНДОКРИННЫЕ КЛЕТКИ

ДИФФЕРЕНЦИРОВКА ЭМБРИОНАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК ЧЕЛОВЕКА В ПАНКРЕАТИЧЕСКИЕ ЭНДОКРИННЫЕ КЛЕТКИ

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

КОМПОЗИЦИИ С УЛУЧШЕННЫМИ Т-КЛЕТКАМИ И СПОСОБЫ

ДИФФЕРЕНЦИРОВКА ЭМБРИОНАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК ЧЕЛОВЕКА В ПАНКРЕАТИЧЕСКИЕ ЭНДОКРИННЫЕ КЛЕТКИ

... 1. Способ индукции экспрессии инсулина в клетках, экспрессирующих гормоны, включающий культивирование клеток панкреатической энтодермы с эфриновым лигандом.2. Способ по п. 2, в котором культивирование клеток панкреатической энтодермы с эфриновым лигандом также усиливает экспрессию ΝΚΧ6.1.3. Способ по п. 2, в котором культивирование клеток панкреатической энтодермы с эфриновым лигандом усиливает экспрессию инсулина и ΝΚΧ6.1 в клетках панкреатической энтодермы по сравнению с экспрессией инсулина и ΝΚΧ6.1 в необработанных клетках панкреатической энтодермы.4. Способ по п. 3, в котором клетки панкреатической энтодермы, по существу, не экспрессируют CDX2 или SOX2.5. Способ по п. 4, в котором клетки панкреатической энтодермы экспрессируют приблизительно менее 10% CDX2 или SOX2.6. Способ по любому из пп. 1-5, в котором эфриновым лигандом является эфрин A3 или эфрин A4.7. Способ по п. 6, в котором клетки панкреатической энтодермы получают путем поэтапной дифференцировки плюрипотентных стволовых ...

Method For Enucleating Nucleated Erythrocyte, And Enucleation Inducer

Provided is a factor capable of inducing enucleation, which is a final stage of erythrocyte differentiation, within a short time. More particularly, provided are a method of inducing enucleation, which is a final stage of erythrocyte differentiation, within a short time by adding a compound derived from proopiomelanocortin (POMC) to an undifferentiated (nucleated) erythrocyte, and an enucleation inducer including the compound.

Treatment method for relapsing-remitting multiple sclerosis

Disclosed is a method for treating relapsing-remitting multiple sclerosis in a patient by administering to the patient autologous, ex vivo-expanded CD4 + CD25 + Foxp3 + CD127 low T reg cells when the patient is in remission. Also disclosed is a method of inhibiting the activity of autoimmune, autologous cytotoxic T and B cells in a patient suffering from relapsing-remitting multiple sclerosis, comprising administering a therapeutically effective amount of autologous CD4 + CD25 − Foxp3 + CD127 low T reg cells to the patient.

MACROPHAGES EAT CANCER CELLS USING THEIR OWN CALRETICULIN AS A GUIDE

Therapeutic and diagnostic methods are provided, which methods relate to the induction of expression of calreticulin on phagocytic cells. Specifically, the methods relate to macrophage-mediated programmed cell removal (PrCR), the methods comprising increasing PrCR by contacting a phagocytic cell with a toll-like receptor (TLR) agonist; or down-regulating PrCR by contacting a phagocytic cell with an inhibitor of Bruton's tyrosine kinase (BTK). In some embodiments, an activator of TLR signaling or a BTK agonist is provided in combination with CD47 blockade. 1. A method of increasing phagocytosis of cancer cells , the method comprising:contacting a population of phagocytic cells with a TLR agonist in a dose effective to increase expression of calreticulin on the phagocytic cell surface; and with an effective dose of a CD47 blocking agent;wherein programmed cell removal of cancer cells by the phagocytic cells is increased.2. The method of claim 1 , wherein the contacting is performed in vivo.3. The method of claim 1 , wherein the contacting is performed in vitro.4. The method of claim 1 , wherein the phagocytic cells are macrophages.5. The method of claim 1 , wherein the TLR agonist is imiquimod.6. The method of claim 1 , wherein the TLR agonist is poly I:C.7. The method of claim 1 , wherein the CD47 blocking agent is an antibody.8. The method of claim 7 , wherein the antibody specifically binds to CD47.9. The method of claim 3 , wherein the phagocytic cells are introduced into a subject following the contacting with a TLR agonist and a CD47 blocking agent.10. The method of claim 9 , wherein expression of calreticulin on the phagocytic cell surface is measured prior to the introducing step.11. A method of protecting blood cells from phagocytosis claim 9 , the method comprising:contacting said cells with a BTK inhibitory agent.12. The method of claim 11 , wherein blood cells in a subject are contacted with a BTK inhibitory agent in vivo.13. The method of claim 12 , ...

Method for Treating Cancer

The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation. 154-. (canceled)55. A T cell composition comprising an engineered T cell expressing a chimeric antigen receptor (CAR) or a T cell receptor (TCR) which specifically binds a clonal neoantigen or a clonal neoantigen peptide.56. The T cell composition according to claim 55 , wherein the TCR is an affinity-enhanced TCR which specifically binds a clonal neoantigen or a clonal neoantigen peptide.57. The T cell composition according to claim 55 , wherein the T cells comprise CD8+ T cells claim 55 , CD4+ T cells or CD8+ and CD4 T+ cells.58. The T cell composition according to claim 55 , wherein the TCR is expressed in autologous T cells from a subject.59. The T cell composition according to which is enriched with engineered T cells that are specific to clonal neoantigens.60. A method for producing a composition comprising engineered T cells claim 55 , the method comprising: ["i) determining mutations present in a sample isolated from the subject's tumour;", 'ii) identifying a clonal mutation which is a mutation present in essentially all tumour cells;', 'iii) identifying a clonal neoantigen, which is an antigen encoded by a sequence which comprises the clonal mutation;', 'vi) identifying a T cell from a sample isolated from the subject which is capable of specifically recognising the clonal neoantigen as a clonal neoantigen-specific T cell;, '(a) identifying a clonal neoantigen-specific T cell from a subject which comprises the steps of(b) isolating a TCR gene that encodes a TCR from the clonal neoantigen-specific T cell; and(c) engineering a T cell ...

NEO-ANTIGEN SPECIFIC T CELLS

The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation. 154-. (canceled)55. A method for identifying a clonal neoantigen-specific T cell which comprises steps of:i) determining mutations present in a sample isolated from a tumour from a subject;ii) identifying a clonal mutation which is a mutation present in essentially all tumour cells;iii) identifying a clonal neoantigen, which is an antigen encoded by a sequence which comprises the clonal mutation; andiv) identifying a T cell from a sample isolated from a subject which is capable of specifically recognising the clonal neoantigen as a clonal neoantigen-specific T cell.56. The method according to wherein the clonal neoantigen-specific T cell is identified using a MHC multimer comprising a clonal neoantigen.57. A method for providing a T cell population which targets a clonal neoantigen in a tumour claim 55 , the method comprising:{'claim-ref': {'@idref': 'CLM-00055', 'claim 55'}, 'i) identifying a T cell from a sample isolated from a subject which is capable of specifically recognising a clonal neoantigen peptide by the method according to ; and'}ii) expanding the T cell to provide a T cell population which targets the clonal neoantigen.58. The method according to claim 57 , wherein in step ii) the T cell is expanded by ex vivo culture with IL-2 or anti-CD3 and/or CD28 antibodies.59. The method according to wherein in step ii) the T cell is co-cultured with irradiated antigen-presenting cells (APCs) claim 57 , artificial antigen presenting cells (aAPCs) or autologous peripheral blood mononuclear cells (PBMCs).60. The method according to claim 57 ...

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* ...

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 ...

METHODS FOR MANUFACTURING T CELLS BY DIRECT SORTING AND COMPOSITIONS THEREOF

Described herein are methods for preparing T cells, including isolating CD8+ T cells from a blood sample obtained from a patient or a donor, culturing the isolated CD8+ T cells in the presence of at least one cytokine, contacting the cultured CD8+ T cells with a multimer containing a target peptide in a complex with an MHC molecule and with at least one binding agent that binds to a T cell surface molecule, in which the multimer is labelled with a first detectable agent and the binding agent is labelled with a second detectable agent, sorting the contacted CD8+ T cells to collect the sorted CD8+ T cells that are detected positive for the first and the second detectable agents, and expanding the collected CD8+ T cells. 1. A method for preparing T cells , comprising wherein the first multimer is labelled with a first detectable agent and the second multimer is labelled with a second detectable agent,', 'wherein the first detectable agent is different from the second detectable agent,', 'wherein the irrelevant peptide has less than 50% sequence identity to the target peptide,, 'contacting CD8+ T cells with a first multimer comprising a target peptide in complex with an MHC molecule and with a second multimer comprising an irrelevant peptide in complex with an MHC molecule,'}sorting the contacted CD8+ T cells to collect sorted CD8+ T cells that are detected positive for the first detectable agent and detected negative for the second detectable agent, andexpanding the collected CD8+ T cells.2. The method of claim 1 , wherein the contacting is performed in the presence of a first binding agent binding to the first detectable agent and/or a second binding agent binding to the second detectable agent.3. The method of claim 2 , wherein the first binding agent and the second binding agent are antibodies.4. The method of claim 1 , wherein the contacting is performed at from about 4° C. to about 37° C.5. The method of claim 1 , wherein the contacting is performed in the ...

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING NEURONAL AND BRAIN TUMORS

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 30 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. 1. A method of treating a patient who has cancer , comprising administering to the patient an effective amount of an antibody specifically binding to an MHC class I or II molecule complexed with a HLA-restricted antigen consisting of the amino acid sequence of KIQEILTQV (SEO ID NO: 14) , wherein the cancer is selected from the group consisting of glioblastoma , renal cell carcinoma , melanoma , endometrial cancer , esophageal squamous cell carcinoma , pancreatic cancer , and urothelial cancer.2. The method of claim 1 , wherein the antibody is a polyclonal antibody claim 1 , a monoclonal antibody claim 1 , or a chimeric antibody.3. The method of claim 1 , wherein the antibody binds to the HLA-restricted antigen with a binding affinity of below 20 nanomolar.4. The method of claim 1 , wherein the antibody binds to the MHC class I molecule complexed with the HLA-restricted antigen.5. The method of claim 1 , wherein the antibody is humanized.6. The method of claim 1 , wherein the effective amount of the antibody is from about 1 μg/kg to about 100 mg/kg of body weight per day.7. The method of claim 1 , wherein the antibody is conjugated with a toxin.8pseudomonas. The method of claim 7 , wherein the toxin is selected from the group consisting of diptheria toxin claim 7 , exotoxin A claim 7 , ...

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 peptide comprising an amino acid sequence selected from the group consisting of (i) SEQ ID No. 1 to SEQ ID No. 489 , and/or a variant sequence thereof which is at least 88% homologous to SEQ ID No. 1 to SEQ ID No. 489 , and wherein said variant binds to molecule(s) of the major histocompatibility complex (MEW) and/or induces T cells cross-reacting with said variant peptide , and/or (ii) a pharmaceutical acceptable salt thereof , wherein said peptide is not a full-length polypeptide.2. The peptide according to claim 1 , wherein said peptide has the ability to bind to an MEW class-I or -II molecule claim 1 , and wherein said peptide claim 1 , when bound to said MEW claim 1 , is capable of being recognized by CD4 and/or COB T cells.3. The peptide 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. 489.4. The peptide according to claim 1 , wherein said peptide has an overall length of from 8 to 100 claim 1 , optionally from 8 to 30 claim 1 , and optionally from 0.8 to 16 amino acids claim 1 , and optionally wherein the peptide consists or consists essentially of an amino acid sequence according to any of SEQ ID No. 1 to SEQ ID No. 489.5. The peptide ...

DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELLS INTO PANCREATIC ENDOCRINE CELLS

The present invention provides methods to promote differentiation of pancreatic endoderm cells to pancreatic endocrine rich clusters and to enhance insulin expression in hormone-expressing cells. 1. A method of enhancing expression of NKX6.1 by treating pancreatic endoderm cells in medium comprising semaphorin 3a or Epigen.2. The method of claim 1 , wherein the population of pancreatic endoderm cells treated with medium comprising semaphorin 3a or Epigen expresses an enhanced amount of NKX6.1 as compared to pancreatic endoderm cells non-treated with medium comprising semaphorin 3a or Epigen.3. The method of claim 1 , wherein the level of expression of insulin claim 1 , glucagon claim 1 , and ghrelin is not affected in pancreatic endoderm cells treated with medium comprising semaphorin 3a or Epigen as compared to pancreatic endoderm cells not treated with medium comprising semaphorin 3a or Epigen.4. The method of claim 1 , wherein the pancreatic endoderm cells are obtained by a stepwise differentiation of pluripotent cells.5. The method of claim 4 , wherein the pluripotent cells wherein the pancreatic endoderm cells are derived from are human pluripotent stem cells.6. The method of claim 5 , wherein the human pluripotent stem cells are human embryonic pluripotent cells.7. The method of claim 1 , wherein the method further comprises:differentiating pluripotent stem cells into definitive endoderm cells;differentiating the definitive endoderm cells into primitive gut tube cells;differentiating the primitive gut tube cells into foregut cells;differentiating the foregut cells into pancreatic foregut precursor cells; anddifferentiating the foregut precursor cells into the pancreatic endoderm cells.8. The method of claim 1 , wherein the method comprises treating pancreatic endoderm cells in medium comprising semaphorin 3a.9. The method of claim 1 , wherein the method comprises treating pancreatic endoderm cells in medium comprising Epigen.10. The method of claim 1 , wherein ...

DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELLS INTO PANCREATIC ENDOCRINE CELLS

The present invention provides methods to promote differentiation of pancreatic endoderm cells to pancreatic endocrine rich clusters and to enhance insulin expression in hormone-expressing cells. 1. A method for inducing formation of endocrine clusters , comprising culturing pancreatic endocrine cells with a sphingosine-1 receptor agonist.2. The method of claim 1 , wherein the sphingosine-1 receptor agonist is sphingosine-1-phosphate (S1P).3. The method of claim 1 , wherein the pancreatic endocrine cells are obtained by a stepwise differentiation of pluripotent stem cells.4. The method of claim 3 , wherein the pluripotent stem cells are human embryonic pluripotent stem cells.5. The method of claim 3 , wherein the pluripotent stem cells are human pluripotent stem cells.6. The method of claim 1 , wherein the method further comprises:differentiating pluripotent stem cells into definitive endoderm cells;differentiating the definitive endoderm cells into primitive gut tube cells;differentiating the primitive gut tube cells into foregut cells;differentiating the foregut cells into pancreatic foregut precursor cells;differentiating the foregut precursor cells into the pancreatic endoderm; anddifferentiating the pancreatic endoderm cells into pancreatic endocrine cells.7. The method of claim 1 , wherein the pancreatic endocrine cells are human pancreatic endocrine cells. The present application is a divisional of U.S. Ser. No. 13/911,829, filed Jun. 6, 2013 (now allowed), which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/657,160, filed Jun. 8, 2012, both of which are incorporated herein by reference in their entirety.The present invention is in the field of cell differentiation. More specifically, the invention discloses use of Ephrin ligands and sphingosine-1-phosphate as regulators of differentiation of pluripotent stem cells to endocrine cells.Advances in cell-replacement therapy for Type I diabetes mellitus and a shortage of transplantable ...

Combination Treatment Of Induced Pluripotent Stem Cells Using Interleukins

Induced pluripotent stem cells are treated using a combination of compounds that improve competence of the induced pluripotent stem cells in responding to differentiation signals and/or improve the efficiency of differentiation of the treated induced pluripotent stem cells in differentiation towards a desired phenotype. The combination treatment can incorporate two or more of prolongation of early G phase, treatment with an interleukin, modulation of DNA methylation, modulation of histone acetylation, and activation of the Wnt pathway. Cells derived from induced pluripotent stem cells so treated can be used in regenerative therapy and production of organoids. 1. A method of generating differentiated cells from induced pluripotent stem cells (iPSCs) , comprising:obtaining a plurality of iPSCs;contacting the plurality of iPSCs with a compound selected to increase duration of early G1 phase in the plurality of iPSCs; andcontacting the plurality of iPSCs with an exogenous interleukin.2. The method of claim 1 , wherein the compound selected to increase duration of early G1 phase in the plurality of iPSCs is an organic solvent.3. The method of claim 2 , wherein the organic solvent is dimethyl sulfoxide.4. The method of claim 1 , wherein the exogenous interleukin is selected to induce differentiation of the plurality of iPSCs toward a pre-selected phenotype.5. The method of claim 4 , wherein the pre-selected phenotype is selected from the group consisting of a blood cell claim 4 , an immune cell claim 4 , a hepatic cell claim 4 , a muscle cell claim 4 , a cardiac cell claim 4 , and a neuron.6. The method of claim 1 , wherein the exogenous interleukin is selected from the group consisting of IL-6 claim 1 , IL-3 claim 1 , IL-1β claim 1 , and IL-14.7. The method of claim 1 , comprising contacting the plurality of iPSCs with a supplementary interleukin.8. The method of claim 1 , comprising contacting the plurality of iPSCs with a soluble IL-6 receptor protein or a hybrid ...

Engager cells for immunotherapy

Embodiments concern methods and/or compositions related to immunotherapy for cancer. In particular embodiments, engager immune cells harbor a vector that encodes a secretable engager molecule. In particular cases, the engager molecule has an activation domain and an antigen recognition domain. In some embodiments, the engager molecules further comprise a cytokine or co-stimulatory domain, for example.

UNIVERSAL DONOR CELLS AND RELATED METHODS

Disclosed herein are universal donor stem cells and cells derived therefrom and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming allogeneic immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor cells disclosed herein are pancreatic endoderm cells that do not express one or more MHC-Class I cell-surface proteins and whose expression of at least one NK activating ligand is disrupted or inhibited. 113-. (canceled)14. A human in vitro cell population comprising:{'sup': −', '+', '+, 'pancreatic endoderm cells (PEC) that are CHGA, NKX6.1, PDX1 pancreatic progenitor cells, and'}{'sup': '+', 'PEC cells that are CHGA pancreatic endocrine cells,'}wherein the function of at least one major histocompatibility complex (MHC)-Class I gene and at least one Natural killer (NK) cell activating ligand is disrupted or inhibited, resulting in reduced binding of the NK activating ligand to a NK activating receptor, in the human in vitro cell population.15. The in vitro cell population of claim 14 , wherein the MHC-Class I gene codes for beta-2 microglobulin (B2M).16. The in vitro cell population of claim 14 , wherein the NK cell activating ligand is Intercellular Adhesion Molecule 1 (ICAM1) claim 14 , CD58 claim 14 , CD155 claim 14 , Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1) claim 14 , Cell Adhesion Molecule 1 (CADM1) claim 14 , MHC-Class I Polypeptide-Related Sequence A (MICA) claim 14 , MHC-Class I Polypeptide-Related Sequence B (MICB) claim 14 , or combinations thereof.17. The in vitro cell population of claim 14 , wherein the NK cell activating ligand is ICAM1 and CD58.18. The in vitro cell population of claim 14 , wherein the NK cell activating ligand is ICAM1 claim 14 , CD58 claim 14 , CD155 claim 14 , CEACAM1 claim 14 , CADM1 claim 14 , MICA and MICB.19. The in vitro cell population of claim 14 , wherein the NK cell activating ligand is ...

IMPROVED MULTIPLE ANTIGEN SPECIFIC CELL THERAPY METHODS

The present invention provides methods of preparing a population of activated T cells by co-culturing T cells with dendritic cells loaded with a plurality of tumor antigen peptides. Also provided are methods of treating cancer in an individual using the activated T cells, pharmaceutical compositions and kits for cell-based cancer immunotherapy. 1. A method of preparing a population of activated T cells , the method comprising:a) contacting a population of dendritic cells with a plurality of tumor antigen peptides to obtain a population of dendritic cells loaded with the plurality of tumor antigen peptides;b) co-culturing the population of dendritic cells loaded with the plurality of tumor antigen peptides and a population of T cells in an initial co-culture medium comprising a plurality of cytokines and an immune checkpoint inhibitor to provide a co-culture; andc) adding an anti-CD3 antibody to the co-culture at about 3 to 7 days after the co-culturing starts, thereby obtaining the population of activated T cells.2. The method of claim 1 , wherein step a) further comprises culturing the population of dendritic cells loaded with the plurality of tumor antigen peptides in a DC maturation medium comprising a toll-like receptor (TLR) agonist.3. The method of claim 2 , wherein the TLR agonist is selected from the group consisting of MPLA claim 2 , Poly I:C claim 2 , resquimod claim 2 , gardiquimod claim 2 , and CL075.4. A method of preparing a population of activated T cells claim 2 , the method comprising:a) contacting a population of dendritic cells with a plurality of tumor antigen peptides to obtain a population of dendritic cells loaded with the plurality of tumor antigen peptides;b) culturing the population of dendritic cells loaded with the plurality of tumor antigen peptides in a DC maturation medium comprising MPLA; andc) co-culturing the population of dendritic cells loaded with the plurality of tumor antigen peptides and a population of T cells, thereby ...

METHOD FOR ACTIVATING AND EXPANDING ISOLATED T CELLS

A method for activating and expanding isolated T cells, the method including adding to isolated T cells ligands presenting microbubbles having a flexible lipid shell with an inner bubble wall enclosing a gas and an outer bubble wall conjugated to ligands capable of achieving cell contact dependent juxtacrine signaling on the isolated T cells; and adding to isolated T cells ligands presenting microbubbles having a flexible lipid shell with an inner bubble wall enclosing a gas and an outer bubble wall conjugated to an antigen capable of forming an immunological synapse (IS) with the T cells. 1. A method for activating and expanding isolated T cells , comprising:a) adding to isolated T cells ligands presenting microbubbles having a flexible lipid shell with an inner bubble wall enclosing a gas and an outer bubble wall conjugated to ligands capable of achieving cell contact dependent juxtacrine signaling on the isolated T cells; andb) adding to isolated T cells ligands presenting microbubbles having a flexible lipid shell with an inner bubble wall enclosing a gas and an outer bubble wall conjugated to an antigen capable of forming an immunological synapse (IS) with the T cells.2. The method of claim 1 , wherein the ligands presenting microbubbles are anti-CD3 and anti-CD28 conjugated microbubbles and the activating and expanding of the isolated T cells is used for preparing the T cells in vitro for adoptive cell transfer.3. The method of claim 2 , wherein preparing the T cells in vitro for adoptive cell transfer is for chimeric antigen receptor (CAR-T) cell therapy.4. The method of claim 1 , wherein the ligands presenting microbubbles are peptide/MHC and anti-CD28 conjugated microbubbles and the activating and expanding of the isolated T cells is used for preparing the T cells in vitro for adoptive cell transfer.5. The method according to claim 1 , further comprising incubating said cells with the ligands presenting microbubbles over a time span that is sufficient for ...

An isolated donor mhc-derived peptide and uses thereof

The invention relates to an peptide derived from a polymorphic region of donor MHC class II molecules which induces tolerance and thus prevents transplant rejection in a patient in need thereof. The invention relates to an isolated peptide of 15 or 16 amino acids long that comprises or consists of the amino acid sequence: REEYARFDSDVGEYR (SEQ ID NO: 1) or a function-conservative variant for use as drug. The invention relates to an in vitro method for determining whether a transplanted patient is tolerant, comprising a step of determining the presence of CD8 + CD45RC low Tregs in a biological sample obtained from said transplanted patient, wherein the presence of CD8 + CD45RC low Tregs is indicative of tolerance.

PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST LUNG CANCER, INCLUDING NSCLC 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 overexpressing a L1RE1 polypeptide comprising SYPAKLSFI (SEQ ID NO: 60) , comprising administering to said patient a population of activated T cells that kill cancer cells ,wherein the activated T cells are cytotoxic CD8+ T cells produced by contacting T cells with an antigen presenting cell that presents a peptide consisting of the amino acid sequence of SEQ ID NO: 60 in a complex with an MHC class I molecule on the surface of the antigen presenting cell in vitro, for a period of time sufficient to activate said T cell,wherein the cancer is lung cancer or liver 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 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 antigen presenting cell is infected with a recombinant virus expressing the peptide.7. The method of claim 6 , wherein the antigen presenting cell is a dendritic cell or a macrophage.8. The method of claim 5 , wherein the ...

DIFFERENTIATED CELL POPULATION OF ENDOTHELIAL CELLS DERIVED FROM HUMAN PLURIPOTENT STEM CELLS, COMPOSITION, SYSTEM, KIT AND USES THEREOF

The present disclosure relates to a differentiated cell population of endothelial cells derived from human pluripotent stem cells. The present invention also relates to a composition, a system and a kit comprising those cells and uses thereof. The present disclosure also described the combination of arterial ECs derived from human pluripotent stem cells with a microfluidic system to create a vascular kit for high-throughput drug screening and/or toxicology analysis. This technology may find particular use for the identification of drugs that may have a fetal cytotoxic effect. 141-. (canceled)42. A method for screening compounds that interfere with embryonic vascular development or has fetal cytotoxic effect , said method comprises providing a system comprising a channel with millimeter or micrometer dimension and a population of differentiated endothelial cells derived from human pluripotent stem cells wherein a portion of the endothelial cells express ephrin B2 , and wherein the endothelial cells are cultured under physiologic shear stress.43. The method of wherein at least 20% of the endothelial cells express ephrin B2.44. The method of wherein 50% to 75% of the endothelial cells express ephrin B2.45. The method of wherein the endothelial cells further express acetylated-low density lipoprotein (“Ac-LDL”).46. The method of wherein the endothelial cells further express at least one of the following genes: Von Willebrand factor (“vWF”) claim 42 , CD31 claim 42 , CD34 claim 42 , vascular endothelial cadherin claim 42 , and Flk-1/KDR.47. The method of wherein the endothelial cells express at least one the following genes: jagged 1 claim 42 , jagged 2 claim 42 , ephrin B1 claim 42 , and Hey-2.48. The method of wherein the endothelial cells express at least one of the following genes: receptor protein tyrosine phosphatase claim 42 , T-cell acute lymphocyte leukemia claim 42 , N-cadherin claim 42 , angiopoietin 1 claim 42 , and DNA-binding protein inhibitor ID-1.49. The ...

Novel peptides and combination of peptides for use in immunotherapy against nhl 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.

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. A peptide consisting of the amino acid sequence of KLAVALLAA (SEQ ID NO: 210) in the form of a pharmaceutically acceptable salt.2. The peptide of claim 1 , wherein the pharmaceutically acceptable salt is a chloride salt claim 1 , acetate salt claim 1 , or trifluoro-acetate salt.3. A pharmaceutical composition comprising the peptide of and an immune-stimulating adjuvant.4. The pharmaceutical composition of claim 3 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody claim 3 , imiquimod claim 3 , resiquimod claim 3 , GM-CSF claim 3 , cyclophosphamide claim 3 , interferon-alpha claim 3 , interferon-beta claim 3 , CpG oligonucleotides and derivatives claim 3 , poly-(I:C) and derivatives claim 3 , RNA claim 3 , sildenafil claim 3 , particulate formulations with poly(lactide co-glycolide) (PLG) claim 3 , virosomes claim 3 , interleukin (IL)-1 claim 3 , IL-2 claim 3 , IL-4 claim 3 , IL-7 claim 3 , IL-12 claim 3 , IL-13 claim 3 , IL-15 claim 3 , IL-21 claim 3 , and IL-23.5. The pharmaceutical composition of claim 15 , wherein the adjuvant comprises IL-2.6. The pharmaceutical composition of claim 15 , wherein the adjuvant comprises IL-7.7. The pharmaceutical composition of claim 15 , wherein the adjuvant comprises IL-15.8. The ...

Regulatory t cell epitopes, compositions and uses thereof

The invention is directed to T cell epitopes wherein said epitopes comprises a peptide or polypeptide chain comprising at least a portion of an immunoglobulin constant or variable region. The invention also relates to methods of using and methods of making the epitopes of the invention.

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

Novel peptides and combination of peptides for use in immunotherapy against 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 peptide comprising an amino acid sequence comprising SEQ ID No. 512 , and variant sequences thereof which are at least 88% homologous to SEQ ID No. 512 , 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 not a full-length polypeptide.2. The peptide or variant according to claim 1 , wherein said peptide has the ability to bind to a 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 the group of SEQ ID No. 512.4. The peptide or variant thereof according to claim 1 , wherein said peptide or variant thereof has an overall length of from 8 to 100 claim 1 , optionally from 8 to 30 claim 1 , and optionally from 8 to 16 amino acids claim 1 , and optionally wherein the peptide consists or consists essentially of an amino acid of SEQ ID No. 512.5. The peptide or variant thereof according to claim 1 , wherein said peptide is part of a ...

METHOD FOR PREPARING AND USING CELL GHOST WITH ACTIVE FACTORS AS SYNERGIST OF LYMPHOCYTE IN VITRO CULTURE

Provided is a method for preparing and using cell ghosts with active factors as a synergist of a lymphocyte in vitro culture. The method for preparing cell ghosts comprises: washing a cell to obtain a washed cell; and cleaving the washed cell to obtain cell ghosts, wherein the cell has cytokines capable of promoting the proliferation and differentiation of lymphocytes on their surface. 1. A method for preparing cell ghosts , comprising:washing cells to obtain washed cells; andlysing the washed cells to obtain the cell ghosts,wherein cytokines capable of promoting lymphocytes proliferation and activation is expressed or attached on the cell surface.2. The method of claim 1 , wherein washing the cells further comprises:suspending the cells in an isotonic solution to obtain cell suspension; andcentrifuging the cell suspension to obtain the washed cells.3. The method of claim 2 , wherein prior to suspending the cells in the isotonic solution claim 2 , the isotonic solution is cooled to 4° C. in advance.4. The method of claim 3 , wherein the isotonic solution is an isotonic phosphate buffer at pH 7.4.5. The method of claim 1 , wherein lysing the washed cells further comprises:suspending the washed cells in a hypotonic solution at a predetermined volume ratio followed by still standing for 2 hours, to obtain cell lysates; andcentrifuging the cell lysates to obtain the cell ghosts.6. The method of claim 5 , wherein the predetermined volume ratio is 1:40.7. The method of claim 5 , wherein prior to suspending the washed cells in the hypotonic solution claim 5 , the hypotonic solution is cooled to 4° C. in advance.8. The method of claim 7 , wherein the hypotonic solution is a hypotonic Tris HCl buffer.9. The method of claim 1 , wherein the cytokines capable of promoting lymphocytes proliferation and activation are at least one selected from a group consisting of IL-4 claim 1 , IL-7 claim 1 , IL-15 claim 1 , IL-21 claim 1 , CD19 claim 1 , CD64 claim 1 , CD86 claim 1 , and 4- ...

COMPOSITIONS FOR THE PREPARATION OF MATURE DENDRITIC CELLS

The invention relates to a method for in vitro maturation of at least one immate dendritic cell, comprising stimulating said immature dendritic cell with TNFα, IL-1β, IFNγ, a TLR7/8 agonist and prostaglandin E2(PG). Furthermore, the invention elates to a composition comprising these factors as well as to mature dendritic cells produced by a method of the invention. 122-. (canceled)23. A mature dendritic cell or a population of mature dendritic cells , obtainable by a method for in vitro maturation of at least one immature dendritic cell , comprising stimulating said immature dendritic cell with TNFα , IL-1β , IFNγ , a TLR7/8 agonist and prostaglandin E2 (PG2).24. The mature dendritic cell or a population of mature dendritic cells of claim 23 , wherein the method further comprises stimulating said immature dendritic cell with a TLR3 agonist.25. The mature dendritic cell or a population of mature dendritic cells of claim 24 , wherein the TLR3 agonist is polyI:C.26. The mature dendritic cell or a population of mature dendritic cells of claim 23 , wherein said substances are part of a composition added to the culture medium of said immature dendritic cell.27. The mature dendritic cell or a population of mature dendritic cells of claim 23 , wherein said TLR7/8 agonist is an imidazoquinilone type immune response modifying compound.28. The mature dendritic cell or a population of mature dendritic cells of claim 27 , wherein said imidazoquinilone type immune response modifying compound is 4-amino-2-ethoxymethyl-α claim 27 ,α-dimethyl-1H-imidazol[4 claim 27 ,5-c]quinoline-1-ethanol (R848).29. The mature dendritic cell or a population of mature dendritic cells of claim 23 , wherein said immature dendritic cell is a monocyte derived immature dendritic cell claim 23 , or wherein said immature dendritic cell is obtained directly from peripheral blood.30. The mature dendritic cell or a population of mature dendritic cells of claim 29 , wherein said immature dendritic cell is ...

Methods for isolating cd8+ selected t cells

A method of producing an engineered T cell population includes obtaining a cell population comprising a CD8+ T cell, isolating the CD8+ T cell from the obtained cell population, activating the isolated CD8+ T cell, introducing a nucleic acid encoding a T cell receptor (TCR) binding to an antigen in a complex with an MHC molecule into the activated CD8+ T cell, and expanding the introduced CD8+ T cell to obtain the engineered T cell population.

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 said patient a population of activated T cells that selectively recognize cells that present a peptide consisting of the amino acid sequence of SPRMSGLLSQT (SEQ ID NO: 226).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( ...

Methods for purifying endoderm and pancreatic endoderm cells derived from human embryonic stem cells

The present disclosure relates to compositions and methods comprising cell surface markers for hES-derived cells, in particular, endoderm lineage cells including pancreatic endoderm-type cells, derived from hES cells.

DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELLS INTO PANCREATIC ENDOCRINE CELLS

The present invention provides methods to promote differentiation of pancreatic endoderm cells to pancreatic endocrine rich clusters and to enhance insulin expression in hormone-expressing cells. 1. A method of inducing insulin expression in hormone-expressing cells comprising culturing pancreatic endoderm cells with an Ephrin ligand.2. The method of claim 2 , wherein culturing the pancreatic endoderm cells with the Ephrin ligand also enhances expression of NKX6.1.3. The method of claim 2 , wherein culturing the pancreatic endoderm cells with an Ephrin ligand enhances expression of insulin and NKX6.1 in the pancreatic endoderm cells when compared with the expression of insulin and NKX6.1 in non-treated pancreatic endoderm cells.4. The method of claim 3 , wherein the pancreatic endoderm cells do not substantially express CDX2 or SOX2.5. The method of claim 4 , wherein the pancreatic endoderm cells express approximately about less than 10% CDX2 or SOX2.6. The method of any one of to claim 4 , wherein the Ephrin ligand is Ephrin A3 or Ephrin A4.7. The method of claim 6 , wherein the pancreatic endoderm cells are obtained by a stepwise differentiation of pluripotent stem cells.8. The method of claim 7 , wherein the pluripotent stem cells are human embryonic pluripotent stem cells.9. The method of claim 7 , wherein the stepwise differentiation comprises differentiating pluripotent stem cells in definitive endoderm cells.10. The method of claim 7 , wherein the stepwise differentiation comprises:differentiating pluripotent stem cells into definitive endoderm cells;differentiating the definitive endoderm cells into primitive gut tube cells;differentiating the primitive gut tube cells into foregut cells;differentiating the foregut cells into pancreatic precursor cells; anddifferentiating the pancreatic precursor cells into pancreatic endoderm cells. The present application is a divisional of U.S. Ser. No. 13/911,829, filed Jun. 6, 2013, which claims the benefit of U.S. ...

Nanoscale Artificial Antigen Presenting Cells

This disclosure provides nano-scale Artificial Antigen Presenting Cells (aAPC), which deliver stimulatory signals to lymphocytes, including cytotoxic lymphocytes, for use as a powerful tool for immunotherapy.

METHOD

The invention concerns a method of generating an immune response in a subject, comprising administering to the subject an antigenic molecule, a photosensitizing agent, a checkpoint inhibitor, and irradiating said subject with light of a wavelength effective to activate the photosensitizing agent to generate an immune response. Preferably the method is a method of vaccination. The invention also provides related methods, compositions, cells, uses, products and kits. 1. A method of generating an immune response in a subject , comprising administering to said subject an antigenic molecule , a photosensitizing agent , a checkpoint inhibitor , and irradiating said subject with light of a wavelength effective to activate said photosensitizing agent , wherein an immune response is generated.2. A method as claimed in wherein the checkpoint inhibitor is an antibody claim 1 , preferably a monoclonal antibody.3. A method as claimed in or wherein the checkpoint inhibitor is selected from anti-CTLA4 and anti-PD-1 claim 1 , preferably (i) anti-CTLA4 and anti-PD-1 or (ii) anti-CTLA4.4. A method as claimed in any one of to wherein the method further comprises contacting said subject with a TLR ligand.5. A method as claimed in wherein said TLR ligand is a TLR3 ligand claim 4 , preferably a double stranded RNA molecule claim 4 , preferably Poly(I:C).6. The method as claimed in any one of to wherein the antigenic molecule is a molecule capable of stimulating an immune response claim 4 , preferably a vaccine antigen or vaccine component and preferably comprises more than one antigen.7. The method as claimed in any one of to wherein the photosensitising agent is selected from TPCS claim 4 , AlPcS claim 4 , TPPSand TPBS claim 4 , preferably TPCS.8. The method as claimed in any one of to wherein the antigenic molecule is a peptide claim 4 , preferably a melanoma peptide or Human Papillomavirus (HPV) peptide.9. The method as claimed in any one of to wherein said method is a method of ...

METHOD FOR INDUCING DIFFERENTIATION OF ALVEOLAR EPITHELIAL CELLS

This invention provides a method for stably producing type II alveolar epithelial cells from pluripotent stem cells. Specifically, the invention relates to a method for producing type II alveolar epithelial cells from pluripotent stem cells comprising steps of: (1) culturing pluripotent stem cells in a medium containing activin A and a GSK3β inhibitor; (2) culturing the cells obtained in Step (1) in a medium containing a BMP inhibitor and a TGFβ inhibitor; (3) culturing the cells obtained in Step (2) in a medium containing BMP4, retinoic acid, and a GSK3β inhibitor; (4) culturing the ventral anterior foregut cells obtained in Step (3) in a medium containing a GSK3β inhibitor, FGF10, KGF, and a NOTCH signal inhibitor; and (5) subjecting the alveolar epithelial progenitor cells obtained in Step (4) to three-dimensional culture in a medium containing a steroid drug, a cAMP derivative, a phosphodiesterase inhibitor, and KGF. 1. A method for producing type II alveolar epithelial cells from pluripotent stem cells comprising Steps (1) to (5) below:(1) culturing pluripotent stem cells in a medium containing activin A and a GSK3β inhibitor;(2) culturing the cells obtained in Step (1) in a medium containing a BMP inhibitor and a TGFβ inhibitor;(3) culturing the cells obtained in Step (2) in a medium containing BMP4, retinoic acid, and a GSK3β inhibitor;(4) culturing the ventral anterior foregut cells obtained in Step (3) in a medium containing a GSK3β inhibitor, FGF10, KGF, and a NOTCH signal inhibitor; and(5) subjecting the alveolar epithelial progenitor cells obtained in Step (4) to three-dimensional culture in a medium containing a steroid drug, a cAMP derivative, a phosphodiesterase inhibitor, and KGF.2. The method according to claim 1 , wherein the GSK3β inhibitor is CHIR99021 claim 1 , the BMP inhibitor is Noggin claim 1 , the TGFβ inhibitor is SB431542 claim 1 , the NOTCH signal inhibitor is DAPT claim 1 , the steroid drug is dexamethasone claim 1 , the cAMP derivative ...

Human facilitating cells

The present disclosure relates to human facilitating cells (hFC), and methods of isolating, characterizing, and using such hFCs.

Novel peptides, combination of peptides and scaffolds for use in immunotherapeutic treatment of various 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.

METHODS FOR ISOLATING AND PROLIFERATING AUTOLOGOUS CANCER ANTIGEN-SPECIFIC CD8+ T CELLS

Provided is a method for isolating and proliferating autologous cancer antigen-specific CD8T cells, and more particularly, a method for selecting an epitope recognized by CD8T cells from autologous cancer antigens present in blood of individual cancer patients; and isolating autologous cancer antigen-specific CD8T cells by using a peptide of the selected epitope, and a method of massively proliferating CD8T cells by using the method. According to the present invention, it is possible to isolate autologous cancer antigen-specific CD8T cells by using the peptide of the CD8 T cell epitope of the autologous cancer antigen present in blood of individual cancer patients instead of a heterologous antigen. Therefore, by using T cells recognizing the autologous cancer antigen, it is possible to effectively select and eliminate cancer cells derived from the cancer patient's own cells. Thus, T cells can be applied to treatment and alleviation of cancer diseases without side effects. 111-. (canceled)12. A method for isolating and expanding an autologous antigen-specific T cells , comprisinga) selecting a CD8+T cell epitope of an autologous cancer antigen present in blood of a cancer patient;b) culturing a peripheral blood mononuclear cell (PBMC) isolated from blood of the cancer patient in a medium together with a peptide of the epitope and IL-2;c) inducing 4-1BB expression in the cultured cells by adding the peptide same as in step b);d) incubating cells in which 4-1BB expression is induced on a culture plate coated with an anti-4-1BB antibody, and then removing unattached cells;{'sup': '+', 'e) suspending autologous cancer antigen-specific CD8T cells isolated in step d), and irradiated allogenic PBMC in a medium comprising IL-2, an anti-CD3 antibody, and autoplasma; and'}{'sup': '+', 'f) expanding the autologous cancer antigen-specific CD8 T cells in step e) by additionally injecting the medium.'}13. The method of claim 12 , wherein the autologous cancer antigen in step a) is ...

GANGLIOSIDES FOR STANDARDIZING AND INCREASING THE SENSITIVITY OF CELLS TO BOTULINUM NEUROTOXINS IN IN VITRO TEST SYSTEMS

The present invention pertains to a method for standardizing the sensitivity of induced pluripotent stem cell (iPS)-derived neurons to a neurotoxin polypeptide, comprising the steps of: a) cultivating different batches of induced pluripotent stem cell-derived neurons in a cell culture medium comprising GT1b for at least 3 hours; b) contacting the different batches of induced pluripotent stem cell-derived neurons of step a) with a neurotoxin polypeptide; c) cultivating the different batches of induced pluripotent stem cell-derived neurons of step b) for at least 24 hours in the presence of GT1b under conditions which allow for the neurotoxin polypeptide to exert its biological activity, thereby standardizing the sensitivity of the induced pluripotent stem cell-derived neurons to a neurotoxin polypeptide. The invention further relates to a method for the generation of induced pluripotent stem cell-derived neurons having a standardized sensitivity to a neurotoxin polypeptide, comprising the steps of: a) providing different batches of induced pluripotent stem cell-derived neurons; b) cultivating the different batches of induced pluripotent stem cell-derived neurons of step a) in a cell culture medium comprising GT1b for at least 3 hours, thereby standardizing the sensitivity of the induced pluripotent stem cell-derived neurons to a neurotoxin polypeptide. In addition, encompassed by the present invention is a method for determining the biological activity of a neurotoxin polypeptide, comprising the steps of: a) cultivating induced pluripotent stem cell-derived neurons in a cell culture medium comprising GT1b for at least 3 hours; b) contacting the induced pluripotent stem cell-derived neurons of step a) with a neurotoxin polypeptide; c) cultivating the induced pluripotent stem cell-derived neurons of step b) for at least 24 hours in the presence of GT1b under conditions which allow for the neurotoxin polypeptide to exert its biological activity; and d) determining the ...

METHOD FOR TREATING CANCER

The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation. 154-. (canceled)55. A method for expanding a T cell population for use in treatment of cancer in a subject , wherein the expanded T cell population targets a neo-antigen , the method comprising steps of:a) providing a sample comprising a T cell population which is capable of specifically recognizing said neo-antigen; andb) co-culturing the T cell population with a composition comprising the neo-antigen, or neo-antigen peptide, and an antigen presenting cell to expand T cells that target the neo-antigen;wherein the neo-antigen has been identified in a sample of a tumour from said subject as being a clonal neo-antigen.56. The method according to wherein said T cells are selectively expanded using a plurality of clonal neo-antigens or clonal neo-antigen peptides that comprise different clonal mutations.57. The method according to claim 56 , wherein said plurality of peptides comprises from 2 to 100 peptides.58. The method according to claim 56 , wherein said expanded T cell population is enriched with T cells which target clonal neo-antigens relative to the starting sample.59. The method according to claim 55 , wherein said antigen presenting cell has been loaded or pulsed with a peptide derived from said clonal neo-antigen.60. The method according to wherein said antigen presenting cell is a dendritic cell.61. The method according to claim 55 , wherein the T cell population is cultured with IL-2 or anti-CD3 and/or CD28 antibodies.62. The method according to claim 55 , wherein the T cell population is isolated from a sample of the tumour of the ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST 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 treating a patient who has 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 consists of the amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 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 a complex with an MHC molecule.7. The method of claim 1 , wherein the ...

Novel peptides and combination of peptides for use in immunotherapy against NHL 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 HLA-A*02+ patient who has cancer , comprising administering to the patient a population of activated antigen-specific CD8+ cytotoxic T cells that kill cancer cells that present at their surface a peptide consisting of the amino acid sequence of GLLQQPPAL (SEQ ID NO: 146) in a complex with an MHC class I molecule ,wherein said cancer is selected from the group consisting of non-Hodgkin lymphomas, chronic lymphocytic leukemia, uterine cancer, lung cancer, kidney cancer, brain cancer, stomach cancer, colon or rectal cancer, liver cancer, prostate cancer, acute myelogenous leukemia, breast cancer, Merkel cell carcinoma (MCC), melanoma, ovarian cancer, esophageal cancer, urinary bladder cancer, endometrial cancer, gall bladder cancer, head and neck cancer, and bile duct cancer.2. The method of claim 1 , wherein the activated antigen-specific CD8+ cytotoxic cells are produced by a method comprising contacting in vitro CD8+ cytotoxic T cells with an antigen presenting cell presenting at its surface a peptide consisting of GLLQQPPAL (SEQ ID NO: 146) in a complex with an MHC class I molecule.3. The method of claim 1 , wherein the T cells are autologous to the patient.4. The method of claim 1 , wherein the T cells are ...

METHODS FOR ENHANCING MATURATION OF CARDIOMYOCYTES

Methods for promoting maturation of cardiomyocytes, involving introducing a microRNA combination containing miR-125b, miR-199a, miR-221, and/or miR222, or suppression of ErbB4 in immature cardiomyocytes, which may be co-cultured with endothelial cells. 1. A method for enhancing cardiomyocyte maturation , the method comprising: (i) transfecting into immature cardiomyocytes one or more microRNA oligonucleotides , which are selected from the group consisting of a miR-125b-5p oligonucleotide , a miR-199a-5p oligonucleotide , a miR-221 oligonucleotide , and a miR-222 oligonucleotide; thereby producing mature cardiomyocytes.2. The method of claim 1 , wherein the method comprises transfecting into the immature cardiomyocytes a combination of the miR-125b-5p oligonucleotide claim 1 , the miR-199a-5p oligonucleotide claim 1 , the miR-221 oligonucleotide claim 1 , and the miR-222 oligonucleotide.3. The method of claim 1 , wherein the immature cardiomyocytes are derived from embryonic stem cells.4. The method of claim 3 , wherein the embryonic stem cells are human embryonic stem cells.5. The method of claim 3 , wherein the embryonic stem cells are mouse embryonic stem cells.6. The method of claim 1 , wherein the immature cardiomyocytes are co-cultured with endothelial cells.7. The method of claim 6 , wherein the immature cardiomyocytes and the endothelial cells are of the same species.8. The method claim 1 , wherein the method further comprising: (ii) measuring the level of major histocompatibility complex (MHC) alpha chain and/or the level of MHC beta chain in the cardiomyocytes after step (i); and (iii) determining the maturation level of the cardiomyocytes based on the level of the MHC alpha chain and/or the level of the MHC beta chain.9. The method of claim 8 , wherein the maturation level of the cardiomyocytes is determined based on the ratio between the level of the MHC alpha chain and the level of the MHC beta chain.10. The method of claim 1 , where the method further ...

Novel peptides and combination of peptides for use in immunotherapy against NHL 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.

Novel peptides and combination of peptides for use in immunotherapy against NHL 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 HLA-A*02+ patient who has cancer , comprising administering to the patient a population of activated antigen-specific CD8+ cytotoxic T cells that kill cancer cells that present at their surface a peptide consisting of the amino acid sequence of KLLNLISKL (SEQ ID NO: 274) in a complex with an MHC class I molecule ,wherein said cancer is selected from the group consisting of non-Hodgkin lymphomas, chronic lymphocytic leukemia, uterine cancer, lung cancer, kidney cancer, brain cancer, stomach cancer, colon or rectal cancer, liver cancer, prostate cancer, acute myelogenous leukemia, breast cancer, Merkel cell carcinoma (MCC), melanoma, ovarian cancer, esophageal cancer, urinary bladder cancer, endometrial cancer, gall bladder cancer, and bile duct cancer.2. The method of claim 1 , wherein the activated antigen-specific CD8+ cytotoxic cells are produced by a method comprising contacting in vitro CD8+ cytotoxic T cells with an antigen presenting cell presenting at its surface a peptide consisting of KLLNLISKL (SEQ ID NO: 274) in a complex with an MHC class I molecule.3. The method of claim 1 , wherein the T cells are autologous to the patient.4. The method of claim 1 , wherein the T cells are obtained from a healthy ...

TUMOR-INFILTRATING LYMPHOCYTES FOR ADOPTIVE CELL THERAPY

Disclosed are compositions and methods for ex vivo expansion of tumorinfiltrating lymphocytes for use in adoptive cell therapy (ACT). Also disclosed are compositions and method for identifying an agent for ex vivo expansion of tumorinfiltrating lymphocytes for use in ACT. Also disclosed are methods for treating cancer using tumor-infiltrating lymphocytes expanded by the disclosed methods. 1. A method for ex vivo expansion of tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT) , comprising culturing the lymphocytes to produce expanded lymphocytes in a culture medium comprising a toll like receptor (TLR) agonist in an amount effective to improve the tumor-specificity of the expanded lymphocytes.2. A method for treating cancer in a subject comprising the steps of:a) obtaining autologous tumor-infiltrating lymphocytes from the subject,b) culturing the lymphocytes in a culture medium comprising a toll like receptor (TLR) agonist to produce expanded lymphocytes,c) treating the subject with nonmyeloablative lymphodepleting chemotherapy, andd) administering the expanded lymphocytes to the mammal.3. The method of claim 1 , wherein the TLR agonist is a ligand for a TLR selected from the group consisting of TLR1 claim 1 , TLR2 claim 1 , TLR3 claim 1 , TLR4 claim 1 , and TLR9.4. The method of claim 1 , wherein the TLR agonist comprises a ligand selected from the group consisting of Pam3CSK4 claim 1 , Pam3CSK4 claim 1 , poly I:C claim 1 , Ribomunyl claim 1 , and CpG ODN.5. The method of claim 1 , wherein the cancer is a solid tumor.6. The method of claim 1 , wherein the cancer is selected from the group consisting of melanoma claim 1 , ovarian cancer claim 1 , breast cancer claim 1 , and colorectal cancer.7. The method of claim 1 , wherein the cancer is metastatic.8. The method of claim 1 , wherein the cancer is recurrent.9. The method of claim 1 , wherein the subject is a human.10. A method for identifying an agent for ex vivo expansion of tumor-infiltrating ...

Isolation Of Bona Fide Pancreatic Progenitor Cells

The present invention relates to a method for isolating bona fide pancreatic progenitor cells and to cell populations enriched for bona fide pancreatic progenitor cells. 2. The method according to claim 1 , wherein the ligands is an antibody or fragment thereof.3. The method according to claim 1 , wherein the cells are removed or selected by flow cytometry.4. The method according to claim 2 , wherein the ligand is an antibody or fragment thereof directed against GP2.5. The method according to claim 4 , further comprising exposing the cell population to an antibody or fragment thereof directed against CD49d and selecting the cells that do not bind to the antibody or fragment thereof directed against CD49d from the cells that do bind the antibody or fragment thereof directed against CD49d prior to exposing the cell population to an antibody directed against GP2.6. The method according to claim 1 , wherein the bona fide pancreatic progenitor cells are derived from cells capable of differentiation selected from human iPS cells (hIPSCs) claim 1 , human ES cells (hESCs) or naive human stem cells (NhSCs).7. The method according to claim 6 , wherein the cells capable of differentiation are derived from cells isolated from an individual.8. The method according to claim 1 , wherein at least one cell of the cell population enriched for bona fide pancreatic progenitor cells has the capability to differentiate further into pancreatic hormone-producing cells.9. The method according to claim 1 , wherein CDKN1a or CDKN2a is inactivated in the cell population provided in i).10. The method according to claim 9 , wherein CDKN1a and/or CDKN2a is inactivated by knock-down claim 9 , deletion claim 9 , silencing or repression.11. The method according to claim 1 , wherein the starting cell population is a pancreatic progenitor population expressing PDX1.12. The method according to claim 11 , wherein inactivation of CDKN1a and/or CDKN2a results in an increase in the proportion of cells ...

Methods of isolating distinct pancreatic cell types

Methods of isolating distinct specific cell types within mixed populations of cells. Methods of isolating specific cell types among pancreatic cells, particularly from human islets of Langerhans. Markers and combinations thereof for use in methods of isolating insulin producing islet beta cells for treatment of diabetes.

M971 CHIMERIC ANTIGEN RECEPTORS

The invention provides a chimeric antigen receptor (CAR) comprising an antigen binding domain comprising SEQ ID NOs: 1-6, a transmembrane domain, and an intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed. 113.-. (canceled)14. A nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising an antigen binding domain comprising the amino acid sequences of SEQ ID NOs: 1-6 , a transmembrane domain , and an intracellular T cell signaling domain.15. The nucleic acid according to claim 14 , comprising a nucleotide sequence comprising SEQ ID NO: 25.16. The nucleic acid according to claim 15 , further comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 26-28.17. A recombinant expression vector comprising the nucleic acid of .18. A host cell comprising the recombinant expression vector of .19. A population of cells comprising at least one host cell of .20. (canceled)21. A pharmaceutical composition comprising the host cell of claim 18 , or a population thereof claim 18 , and a pharmaceutically acceptable carrier.22. (canceled)23. A method of treating or preventing cancer in a mammal claim 18 , the method comprising administering to the mammal a host cell of claim 18 , or a population thereof claim 18 , in an amount effective to treat or prevent cancer in the mammal. This application claims the benefit of U.S. Provisional Application No. 61/717,960, filed on Oct. 24, 2012, the entire contents of which are incorporated herein by reference.Incorporated by reference in its entirety herein is a computer-readable nucleotide/amino acid sequence listing submitted concurrently herewith and identified as ...

SELECTION OF HUMAN HEMATOPOETIC STEM CELLS USING EPCR

It is provided a method of expanding ex vivo hematopoietic stem cells (HSC), the method comprising selecting a population of Endothelial Protein C Receptor (EPCR) HSC, culturing the selected HSC thereby expanding said EPCR HSC and the use of the expanded EPCR HSC for stem cells transplantation. 1: A method of expanding ex vivo stem and/or progenitor cells , the method comprising selecting a population of Endothelial Protein C Receptor (EPCR) cells from a starting population of stem and/or progenitor cells , and culturing the selected EPCR cells thereby expanding said EPCR cells.2: The method of claim 1 , wherein the stem and progenitor cells are human hematopoietic stem and progenitor cells.3: The method of claim 2 , wherein the hematopoietic stem and progenitor cells are from umbilical cord blood cells claim 2 , mobilized peripheral blood cells claim 2 , or bone marrow cells.4: The method of claim 2 , wherein the hematopoietic stem and progenitor cells are mobilized peripheral blood cells.5: The method of claim 2 , wherein the hematopoietic stem and progenitor cells are from human cord blood cells.6: The method of claim 1 , wherein said EPCR cells are further enriched prior or after the selecting of the EPCR cells by harvesting CD34 claim 1 , CD38 claim 1 , CD90 claim 1 , CD45RA claim 1 , CD133 and/or CD49f cells.7: The method of claim 6 , wherein said selected EPCR+ cells are CD34CD45RA cells.8: The method of claim 2 , wherein said hematopoietic stem cells are short and long term hematopoietic stem cells.9: The method of claim 1 , further comprising the step of stimulating the starting population with at least one cell expanding factor.10: The method of claim 9 , wherein the at least one cell expanding factor is UM171 claim 9 , UM729 claim 9 , analogues thereof claim 9 , lenalidomide claim 9 , thalidomide or a combination thereof.11: The method of claim 10 , further comprising stimulating the starting population with at least one cell expanding factor in ...

PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST NON-SMALL CELL LUNG CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of treating a patient who has cancer , comprising administering to the 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 SEQ ID NO: 1-24 ,wherein the activated T cells are produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell,wherein said cancer is selected from the group consisting of non-small cell lung cancer, hepatocellular cancer, head and neck cancer, and ovarian 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 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 5 , wherein the expansion is in the presence of an anti-CD3 antibody claim 5 , an anti-CD28 antibody claim 5 , and IL-2.7. The method of claim 1 , wherein the MHC class I molecule is HLA-A*02.8. The method of claim 1 , wherein the contacting is in ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST 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.

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.

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST LUNG CANCER, INCLUDING NSCLC 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 overexpressing a COL12A1 polypeptide comprising SYSIGIANF (SEQ ID NO: 57) , comprising administering to said patient a population of activated T cells that kill cancer cells ,wherein the activated T cells are cytotoxic CD8+ T cells produced by contacting T cells with an antigen presenting cell that presents a peptide consisting of the amino acid sequence of SYSIGIANF (SEQ ID NO: 57) in a complex with an MHC class I molecule on the surface of the antigen presenting cell in vitro, for a period of time sufficient to activate said T cell,wherein the cancer is lung cancer or brain 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 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 antigen presenting cell is infected with a recombinant virus expressing the peptide.7. The method of claim 6 , wherein the antigen presenting cell is a dendritic cell or a macrophage.8. The method of claim 5 , ...

Primed Cardiac Progenitors and Methods for Making and Using Same

An improvement to the GiWi protocol for differentiating human pluripotent cells to developmentally mature cardiomyocytes includes a step of activating innate immunity in mesoderm stage cells in the in vitro differentiation culture. When the mesoderm cells, which are precursors to cardiac progenitor cells, are primed by exposure to an activator of innate immunity, a population of cardiomyocytes is generated that is more developmentally mature than is generated in the GiWi protocol without the primed step. Also provided herein are in vitro ventricular conductive microtissues and isolated, in vitro populations of ventricular conduction system-like cells and methods for making the same. 1. A method for producing a population of primed cardiac progenitors from pluripotent stem cells , comprising the steps of:(i) activating Wnt/β-catenin signaling in cultured pluripotent stem cells to obtain a first cell population;(ii) culturing the first cell population for a period following the end of the activating step until cardiac mesoderm cells are present in the first cell population; and(iii) after the culturing period in step (ii), inhibiting Wnt/β-catenin signaling in the cardiac mesoderm cells in the presence of an activator of innate immunity until a second cell population comprising primed cardiac progenitors is produced.2. The method according to claim 1 , wherein the activator of innate immunity is a Toll-like Receptor 3 ligand or NF-κB activator.3. The method of claim 1 , wherein the Toll-like Receptor 3 ligand is mimetic of a double stranded RNA.4. The method according to claim 3 , wherein the mimetic is polyinosinic-polycytidylic acid (pI:C).5. The method according to claim 1 , wherein the activator of innate immunity is provided to the cultured first cell population for two days.6. An isolated claim 1 , in vitro population of primed cardiac progenitors produced according to the method of .7. A method for generating a population of developmentally mature ...

METHODS FOR MANUFACTURING T CELLS EXPRESSING OF CHIMERIC ANTIGEN RECEPTORS AND OTHER RECEPTORS

A method for manufacturing T cell populations enriched for cells expressing CD27 and useful in T cell therapy is described. The T cell populations are also useful for a variety of purposes requiring a highly active, long-lived T cell population. Such cells elicit a superior antitumor immune response in vitro and in vivo. 1. A method for preparing a population T cells comprising CD27+ cells expressing a recombinant T cell receptor , comprising:(a) providing a population of human T cells;(b) treating the human T cell population to enrich for CD27+ cells thereby providing a population of T cells that is enriched for CD27+ cells relative to the provided human T cell population; and(c) introducing a nucleic acid molecule expressing a recombinant T cell receptor into the population of cells that are enriched for CD27+ cells relative to the provided T cell population thereby providing population of T cells comprising CD27+ cells expressing a recombinant T cell receptor.2. A method for preparing a population T cells expressing a recombinant T cell receptor , comprising:(a) providing a population of human T cells;(b) introducing a nucleic acid molecule expressing a recombinant T cell receptor into the provided population of human T cells thereby providing a population of T cells expressing a recombinant T cell receptor; and(c) treating the population of T cells expressing a recombinant T cell receptor to enrich the population for CD27+ cells thereby providing a population of T cells comprising CD27+ cells expressing a recombinant T cell receptor.3. The method of claim 1 , wherein the step of providing a population of human T cells comprises:(a) providing a population of human T cells;(b) treating the provided population of human T cells to deplete CD14+ cells and CD25+ cells and thereby providing a population of human T cells; and(c) optionally, treating the population of human T cells to enrich for CD62L+ cells.4. The method of claim 1 , wherein the step of providing a ...

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 cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells that aberrantly present a peptide consisting of the amino acid sequence of SYVKVLHHL (SEQ ID NO: 490) ,wherein said cancer is selected from the group consisting of lung cancer, acute myeloid leukemia, breast cancer, bile duct cancer, brain cancer, chronic lymphocytic leukemia, colorectal carcinoma, esophageal cancer, gallbladder cancer, gastric cancer, head and neck squamous cell carcinoma, hepatocellular cancer, melanoma, non-Hodgkin lymphoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cell cancer, urinary bladder cancer, and uterine 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 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 ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST 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 population of activated T cells that selectively recognize cells that aberrantly present a peptide consisting of the amino acid sequence of KITDTLIHL (SEQ ID NO: 266) ,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 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 ...

Methods for manufacturing t cells expressing of chimeric antigen receptors and other receptors

A method for preparing T cell populations for use in CAR T cell therapy and other immune cell therapies is described.

Genomic engineering of pluripotent cells

Provided are methods and compositions for obtaining genome-engineered iPSCs, and derivative cells with stable and functional genome editing at selected sites. Also provided are cell populations or clonal cell lines derived from genome-engineered iPSCs, which comprise targeted integration of one or more exogenous polynucleotides, and/or in/dels in one or more selected endogenous genes.

HEMATOPOIETIC PROGENITOR CELL MARKER

Provided is a method for producing a CD4/CD8 double positive cell, including the following steps: 1. A method for producing CD4/CD8 double positive cells , the method comprising the following steps:step 1: separating, from a cell population comprising hematopoietic progenitor cells, cells expressing one or more kinds of molecules selected from the first group consisting of CD24, CD62L, CD90, CD143, CD263, Notch3, CD32, CD39, CD49a, CD164, CD317, CD200, CD218a, CD7, CD144, CD56, CD226, CD262 and CD325, and/or a cell not expressing one or more kinds of molecules selected from the second group consisting of CD49f, CD51, CD102, CD42b, CD61, CD62P, CD69, CD102 and CD156c, andstep 2: differentiating the cell separated in step 1 into CD4/CD8 double positive cells.2. The method according to claim 1 , wherein the cells selected in said step 1 do not express CD235a or CD14 but express CD45 claim 1 , CD34 and CD43.3. The method according to claim 1 , wherein said step 1 comprises separating claim 1 , from a cell population comprising hematopoietic progenitor cells claim 1 , cells expressing one or more kinds of molecules selected from the first group consisting of CD24 claim 1 , CD62L claim 1 , CD90 claim 1 , CD143 claim 1 , CD263 claim 1 , Notch3 claim 1 , CD32 claim 1 , CD39 claim 1 , CD49a claim 1 , CD164 claim 1 , CD317 claim 1 , CD200 claim 1 , CD218a claim 1 , CD7 claim 1 , CD144 claim 1 , CD56 claim 1 , CD226 claim 1 , CD262 and CD325.4. The method according to claim 3 , wherein the first group in said step 1 consists of CD24 claim 3 , CD62L claim 3 , CD90 claim 3 , CD143 claim 3 , CD263 claim 3 , Notch3 claim 3 , CD200 claim 3 , CD218a claim 3 , CD7 and CD144.5. The method according to claim 1 , wherein said step 1 comprises separating claim 1 , from a cell population comprising hematopoietic progenitor cells claim 1 , cells not expressing one or more kinds of molecules selected from the second group consisting of CD49f claim 1 , CD51 claim 1 , CD102 claim 1 , CD42b ...

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 cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells that aberrantly present a peptide consisting of the amino acid sequence of GLLEDERALQL (SEQ ID NO: 518) ,wherein said cancer is selected from the group consisting of lung cancer, acute myeloid leukemia, breast cancer, bile duct cancer, brain cancer, chronic lymphocytic leukemia, colorectal carcinoma, esophageal cancer, gallbladder cancer, gastric cancer, head and neck squamous cell carcinoma, hepatocellular cancer, melanoma, non-Hodgkin lymphoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cell cancer, urinary bladder cancer, and uterine 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 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 ...

Methods of producing and using regulatory b-cells

The invention is directed to a method of preparing B-cells that produce interleukin-10 (IL-10), or IL-10 per se, which comprises contacting one or more B-cells ex vivo with an isolated interleukin-35 (IL-35) protein, and culturing the one or more B-cells under conditions to provide one or more B-cells that produce IL-10. The invention also is directed to a method of suppressing the proliferation of lymphocytes in vitro or in vivo by contacting lymphocytes with an isolated IL-35 protein. The invention further is directed to a method of suppressing autoimmunity in a mammal by administering to the mammal an IL-35 protein or IL-10-producing B-cells.

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 treating a patient who has lung cancer , comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of MEVDPIGHVYIF (SEQ ID NO: 320).2. The method of claim 1 , wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell claim 1 , for a period of time sufficient to activate said T cell.3. The method of claim 1 , wherein the T cells are autologous to the patient.4. The method of claim 1 , further comprising administering to said patient an adjuvant selected from anti-CD40 antibody claim 1 , imiquimod claim 1 , resiquimod claim 1 , GM-CSF claim 1 , cyclophosphamide claim 1 , sunitinib claim 1 , bevacizumab claim 1 , interferon-alpha claim 1 , interferon-beta claim 1 , CpG oligonucleotides and derivatives claim 1 , poly-(I:C) and derivatives claim 1 , RNA claim 1 , sildenafil claim 1 , particulate formulations with poly(lactide co-glycolide) (PLG) claim 1 , virosomes claim 1 , interleukin (IL)-1 claim 1 , IL-2 claim 1 , IL-4 claim 1 , IL-7 claim 1 , IL-12 claim 1 , IL-13 claim 1 , IL-15 ...

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.

Methods for Treatment of HIV and Other Infections Using a T-Cell or Viral Activator and Anti-Retroviral Combination Therapy

Disclosed is a method for treating infection with a pathogen. The method involves administration of (1) a substance which induces active pathogen replication in a cell latently infected with HIV and (2) an anti-pathogen drug. Also disclosed are methods for expanding CD+ T cells from peripheral blood mononuclear cells isolated from human subjects in the presence of an antiretroviral drug and for treating HIV infection by infusing the expanded CD4+ cells into HIV-infected patients.

Compositions comprising regulatory t cells and methods of making and using the same

Provided herein are populations of ex vivo expanded umbilical cord blood-derived regulatory T cells. Also provided are methods of making and using the same.

Anti-lilrb antibodies and uses thereof

Disclosed herein are specific and pan antibodies that interact with one or more members of the LILRB receptor family. In some instances, also described herein are pharmaceutical compositions that comprise one or more anti-LILRB antibodies and methods of modulating inflammatory macrophage activation, lymphocyte activation, and phagocytosis.

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST LUNG CANCER, INCLUDING NSCLC 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 overexpressing an MMP12 polypeptide comprising the amino acid sequence of SEQ ID NO: 24 , comprising administering to said patient a population of activated T cells that kill cancer cells ,wherein the activated T cells are cytotoxic CD8+ T cells produced by contacting T cells with an antigen presenting cell that presents a peptide consisting of the amino acid sequence of SEQ ID NO: 24 in a complex with an MHC class I molecule on the surface of the antigen presenting cell in vitro, for a period of time sufficient to activate said T cell.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 antigen presenting cell is infected with a recombinant virus expressing the peptide.7. The method of claim 6 , wherein the antigen presenting cell is a dendritic cell or a macrophage.8. The method of claim 5 , wherein the expansion is in the presence of ...

PEPTIDES AND T CELLS FOR USE IN IMMUNOTHERAPEUTIC TREATMENT OF VARIOUS 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 peptide consisting of the amino acid sequence TLDEYLTYL (SEQ ID NO: 80) 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-(1:C) and derivatives claim 5 , RNA claim 5 , sildenafil claim 5 , particulate formulations ...

Pluripotent cell lines and methods of use thereof

Methods of generating cell lines with a sequence variation or copy number variation of a gene of interest, methods of use thereof, and cell lines with a sequence variation or copy number variation of a gene of interest are provided.

METHODS OF MANUFACTURING CAR-T CELLS

Aspects of the present disclosure relate to methods for manufacturing genetically engineered T cells expressing a chimeric antigen receptor (CAR) that provide several improvements over conventional manufacturing methods, thereby enabling production of a robust supply of clinically useful CAR T-cell therapies. 1. A method for manufacturing genetically engineered T cells , the method comprising:(i) providing a first population of T cells;(ii) introducing into the first population of T cells a first ribonucleoprotein (RNP) complex comprising a first Cas9 enzyme and a first guide RNA (gRNA) targeting a CD70 gene to produce a second population of T cells, wherein the second population of T cells comprises T cells having the CD70 gene disrupted;(iii) introducing into the second population of T cells a second RNP complex comprising a second Cas9 enzyme and a second gRNA targeting a T cell receptor alpha chain constant region (TRAC) gene, and a third RNP complex comprising a third Cas9 enzyme and a third gRNA targeting a beta-2 microglobulin (β2M) gene to produce a third population of T cells, wherein the third population of T cells comprises T cells having the CD70 gene disrupted, the TRAC gene disrupted, and the β2M gene disrupted;(iv) incubating the third population of T cells with an adeno-associated viral (AAV) vector to produce a fourth population of T cells, wherein the AAV vector comprises a nucleic acid sequence encoding a chimeric antigen receptor (CAR) and wherein the nucleic acid sequence is flanked by homologous sequences to the TRAC gene, and wherein the fourth population of T cells comprises activated T cells expressing the CAR and having the CD70 gene disrupted, the TRAC gene disrupted, and the β2M gene disrupted;(v) expanding the fourth population of T cells thereby producing an expanded T cell population;{'sup': '+', '(vi) removing TCRαβ T cells from the expanded T cell population to produce a population of genetically engineered T cells, wherein the ...

Novel immunotherapy against several tumors including neuronal and brain tumors

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 30 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.

ENGAGER CELLS FOR IMMUNOTHERAPY

Embodiments concern methods and/or compositions related to immunotherapy for cancer. In particular embodiments, engager immune cells harbor a vector that encodes a secretable engager molecule. In particular cases, the engager molecule has an activation domain and an antigen recognition domain. In some embodiments, the engager molecules further comprise a cytokine or co-stimulatory domain, for example. 1. A cell comprising a polynucleotide vector encoding a bipartite molecule comprising an activation domain that binds to one or more cell surface molecules and an antigen recognition domain that binds to EphA2 and/or CD19.2. The cell of claim 1 , wherein the activation domain claim 1 , antigen recognition domain claim 1 , or both domains comprise single chain fragment variable (scFV) antibody moieties.3. The cell of claim 1 , wherein the activation domain is a scFV that recognizes a molecule selected from the group consisting of CD3 claim 1 , CD16 claim 1 , CD27 claim 1 , CD28 claim 1 , CD40 claim 1 , CD134 claim 1 , and CD137.4. The cell of claim 1 , wherein the vector is a non-viral or viral vector.5. The cell of claim 4 , wherein the viral vector is selected from the group consisting of lentiviral claim 4 , adenoviral claim 4 , retroviral claim 4 , and adeno-associated viral vector.6. The cell of claim 1 , wherein the vector is an oncolytic vector.7. A method of treating an individual with cancer claim 1 , comprising the step of delivering a therapeutically effective amount of one or more cells of to the individual.8. The method of claim 7 , wherein the cancer is EphA2-positive or CD19-positive.9. The method of claim 7 , wherein the vector is selected from the group consisting of lentiviral claim 7 , adenoviral claim 7 , retroviral claim 7 , and adeno-associated viral vector.10. The method of claim 7 , wherein the individual is provided with an additional cancer therapy.11. The method of claim 10 , wherein the additional cancer therapy is surgery claim 10 , ...

METHODS AND COMPOSITIONS FOR NATURAL KILLER CELLS

The application provides new compositions and methods for stimulating the production of natural killer (NK) cells in a subject. NK cells can be selectively expanded with a combination of stimulating ligands. Methods and compositions for the administration of stimulatory ligands modified to self-insert into tumor cells, thereby stimulating an increase in the number of NK cells in proximity to a tumor, are also described. 174-. (canceled)75. A NK cell expanding composition free of feeder cells and comprising at least one plasma membrane vesicle purified from NK cell feeder cells transfected with at least two NK cell effector agents , wherein one of the at least two NK cell effector agents is IL-21.76. A NK cell expanding composition comprising an effective amount of plasma membrane vesicles purified from NK cell feeder cells transfected with at least two NK cell effector agents , wherein one of the at least two NK cell effector agents is IL-21 , in a medium lacking feeder cells.77. The composition of claim 75 , wherein one of the at least two NK cell effector agents is 41BBL.78. The composition of claim 75 , further comprising at least one additional NK cell effector agent claim 75 , wherein the at least one additional NK cell effector agent is a cytokine claim 75 , an adhesion molecule claim 75 , or an NK cell activating agent.79. The composition of claim 78 , wherein the at least one additional NK cell effector agent is IL-15 claim 78 , IL-2 claim 78 , IL-12 claim 78 , IL-18 claim 78 , IL-2 claim 78 , MICA claim 78 , 2B4 claim 78 , LFA-1 claim 78 , or BCM1/SLAMF2.80. (canceled)81. (canceled)82. The composition of claim 75 , further comprising a second plasma membrane vesicle claim 75 , wherein the second plasma membrane vesicle comprises at least one additional NK cell effector agent.83. The composition of claim 75 , further comprising a membrane self-inserting peptide that promotes insertion into a membrane claim 75 , the membrane self-inserting peptide conjugated ...

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 treating a patient who has lung cancer , comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of VWSDVTPLNF (SEQ ID NO: 10).2. The method of claim 1 , wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell claim 1 , for a period of time sufficient to activate said T cell.3. The method of claim 1 , wherein the T cells are autologous to the patient.4. The method of claim 1 , further comprising administering to said patient an adjuvant selected from anti-CD40 antibody claim 1 , imiquimod claim 1 , resiquimod claim 1 , GM-CSF claim 1 , cyclophosphamide claim 1 , sunitinib claim 1 , bevacizumab claim 1 , interferon-alpha claim 1 , interferon-beta claim 1 , CpG oligonucleotides and derivatives claim 1 , poly-(I:C) and derivatives claim 1 , RNA claim 1 , sildenafil claim 1 , particulate formulations with poly(lactide co-glycolide) (PLG) claim 1 , virosomes claim 1 , interleukin (IL)-1 claim 1 , IL-2 claim 1 , IL-4 claim 1 , IL-7 claim 1 , IL-12 claim 1 , IL-13 claim 1 , IL-15 ...

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 treating a patient who has lung cancer , comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of SYNGYVFYL (SEQ ID NO: 25).2. The method of claim 1 , wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell claim 1 , for a period of time sufficient to activate said T cell.3. The method of claim 1 , wherein the T cells are autologous to the patient.4. The method of claim 1 , further comprising administering to said patient an adjuvant selected from anti-CD40 antibody claim 1 , imiquimod claim 1 , resiquimod claim 1 , GM-CSF claim 1 , cyclophosphamide claim 1 , sunitinib claim 1 , bevacizumab claim 1 , interferon-alpha claim 1 , interferon-beta claim 1 , CpG oligonucleotides and derivatives claim 1 , poly-(I:C) and derivatives claim 1 , RNA claim 1 , sildenafil claim 1 , particulate formulations with poly(lactide co-glycolide) (PLG) claim 1 , virosomes claim 1 , interleukin (IL)-1 claim 1 , IL-2 claim 1 , IL-4 claim 1 , IL-7 claim 1 , IL-12 claim 1 , IL-13 claim 1 , IL-15 ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST NHL 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 peptide consisting of the amino acid sequence FVIDSFEEL (SEQ ID NO: 113) 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-1 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 is chloride salt.4. The peptide of claim 1 , wherein the pharmaceutically acceptable 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 claim 5 , sildenafil claim 5 , particulate formulations with poly( ...

Administration of Angiocidin for the Treatment of Cancer

Methods are presented for the therapeutic administration of angiocidin in the treatment of cancers such as glioma, breast cancer, and leukemia. Methods are also presented for inducing growth arrest and/or apoptosis of tumor cells, as well as inducing differentiation of tumor cells to inhibit tumorigenicity and to confer a non-tumor or healthy phenotype.

NOVEL PEPTIDES, COMBINATION OF PEPTIDES AND SCAFFOLDS FOR USE IN IMMUNOTHERAPEUTIC TREATMENT OF VARIOUS 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 peptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 1 to SEQ ID No. 388 , and variant sequences thereof that are at least 88% homologous to SEQ ID No. 1 to SEQ ID No. 388 , 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 not a full-length polypeptide.2. The peptide 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 or 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. 388.4. The peptide or variant thereof according to any of to claim 1 , wherein said peptide or variant thereof has an overall length of from 8 to 100 claim 1 , preferably from 8 to 30 claim 1 , and more preferred from 8 to 16 amino acids claim 1 , and most preferred wherein the peptide consists or consists essentially of an amino acid sequence according to ...

Tumor-infiltrating lymphocytes for adoptive cell therapy

Disclosed are compositions and methods for ex vivo expansion of tumorinfiltrating lymphocytes for use in adoptive cell therapy (ACT). Also disclosed are compositions and method for identifying an agent for ex vivo expansion of tumorinfiltrating lymphocytes for use in ACT. Also disclosed are methods for treating cancer using tumor-infiltrating lymphocytes expanded by the disclosed methods.

METHODS OF MAKING CHIMERIC ANTIGEN RECEPTOR?EXPRESSING CELLS

The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions generated by such methods. 1. A method of making a population of cells (e.g. , T cells) that express a chimeric antigen receptor (CAR) , the method comprising:(i) contacting a population of cells (e.g., T cells) with IL-2 and one or both of: IL-15 and IL-21, and(ii) contacting the population of cells (e.g., T cells) with a nucleic acid molecule (e.g., a DNA or RNA molecule) encoding the CAR, thereby providing a population of cells (e.g., T cells) comprising the nucleic acid molecule, wherein:the population of cells at the beginning of step (i) has one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or all) of the following properties:(1) the population of cells at the beginning of step (i) does not expand or expands for no more than 5, 6, 7, 8, or 9-fold over 8-11 days using the Bead CART cell manufacturing process described in Example 1,(2) the percentage of naïve T cells and/or stem cell-like memory T cells (Tscm) among T cells, the percentage of CD4+ naïve T cells and/or Tscm cells among CD4+ T cells, or the percentage of CD8+ naïve T cells and/or Tscm cells among CD8+ T cells in the population of cells at the beginning of step (i) is lower than 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, or 60%, e.g., lower than 10%,(3) the percentage of naïve T cells and/or Tscm among T cells, the percentage of CD4+ naïve T cells and/or Tscm cells among CD4+ T cells, or the percentage of CD8+ naïve T cells and/or Tscm cells among CD8+ T cells in the population of cells at the beginning of step (i) is lower than the corresponding value in a reference population of cells (e.g., a population of cells from a healthy donor, or a population of cells that expands more than 10, 15, or 20-fold over 8-11 days using the Bead CAR T cell manufacturing process described in Example 1), e.g., at least 20, 30, 40, 50, 60, 70, 80, or ...

Dendritic Cell Immune Receptor Activator, Method for Activating Dendritic Cell Immune Receptor, Osteoclast Formation Inhibitor, Method for Inhibiting Osteoclast Formation, Dendritic Cell Differentiation/Proliferation Inhibitor, Method for Inhibiting Dendritic Cell Differentiation/Proliferation, Cytokine Production Inhibitor, Method for Inhibiting Cytokine Production, Therapeutic Method and Screening Method

A dendritic cell immune receptor activator, comprising a compound having a sugar chain as an active ingredient, the sugar chain having a basic structure represented by the following formula: 110.-. (canceled)121. The method for activating a dendritic cell immune receptor according to claim , wherein osteoclast formation is inhibited by causing the dendritic cell immune receptor activator to contact the dendritic cell immune receptor of the cell.131. The method for activating a dendritic cell immune receptor according to claim , wherein dendritic cell differentiation/proliferation is inhibited by causing the dendritic cell immune receptor activator to contact the dendritic cell immune receptor of the cell.141. The method for activating a dendritic cell immune receptor according to claim , wherein cytokine production is inhibited by causing the dendritic cell immune receptor activator to contact the dendritic cell immune receptor of the cell. The invention relates to a dendritic cell immune receptor activator, a method for activating a dendritic cell immune receptor, an osteoclast formation inhibitor, a method for inhibiting osteoclast formation, a dendritic cell differentiation/proliferation inhibitor, a method for inhibiting dendritic cell differentiation/proliferation, a cytokine production inhibitor, a method for inhibiting cytokine production, a therapeutic method, and a screening method.A dendritic cell immune receptor (hereinafter, also referred to as DCIR) is a membrane protein that expresses in a cell such as a dendritic cell, which is a major antigen presentation cell, and an osteoclastic cell, which is a bone resorption cell. A DCIR has a carbohydrate-recognition domain (CRD) in the extracellular region, and an immunoreceptory tyrosine-based inhibitory motif (ITIM) in the intracellular region.The inventors have succeeded in preparing a mouse lacking a gene of a DCIR (Dcir−/− mouse), and reported that the mouse spontaneously develops with aging autoimmune ...

NATURAL KILLER CELL PRIMING COMPOSITION

The present invention relates to a composition for priming a human Natural Killer (NK) cell. The present invention provides a natural killer (NK) cell priming composition which comprises (i) a CD2 ligation agent; (ii) an NKp46 ligation agent; and (iii) an LFA-1 ligation agent. The present invention also provides an NK-cell priming substrate which comprises (i) a CD2 ligation agent; (ii) an NKp46 ligation agent; and (iii) an LFA-1 ligation agent. 1. A natural killer (NK) cell priming composition which comprises (i) a CD2 ligation agent; (ii) an NKp46 ligation agent; and (iii) an LFA-1 ligation agent.2. The NK-cell priming composition according to claim 1 , wherein the CD2 ligation agent is an anti-CD2 antibody or an oligonucleotide aptamer.3. (canceled)4. The NK-cell priming composition according to claim 1 , wherein the NKp46 ligation agent is an anti-NKp46 antibody or an oligonucleotide aptamer.5. (canceled)6. The NK-cell priming composition according to claim 1 , wherein the LFA-1 ligation agent is an anti-LFA-1 antibody or an oligonucleotide aptamer.7. (canceled)8. The NK-cell priming substrate which comprises a CD2 ligation agent claim 1 , an NKp46 ligation agent and a LFA-1 ligation agent according to .9. The NK-cell priming substrate according to which comprises a three-dimensional surface coated with the CD2 ligation agent claim 8 , the NKp46 ligation agent and the LFA-1 ligation agent.10. The NK-cell priming substrate according to claim 9 , wherein the three-dimensional surface is a bead.11. The NK-cell priming substrate according to claim 10 , wherein the bead is an anti-biotin bead.12. A method of priming NK-cells which comprises the step of contacting human resting NK (rNK) cells with:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'An NK-cell priming composition according to .'}13. The method according to claim 12 , in which the rNK-cell is obtained from a patient.14. A population of primed NK-cells produced by the method of .15. The population of ...

Use of mcoln-1 modulators to regulate cell migration

The present invention relates to the use of modulators of Mcoln-1 for modulating the cells migration, in particular the migration of dendritic cells and tumor cells, especially for antitumoral vaccination, autoimmune diseases treatment, and metastasis prevention.

METHODS AND COMPOSITIONS FOR NATURAL KILLER CELLS

The application provides new compositions and methods for stimulating the production of natural killer (NK) cells in a subject. NK cells can be selectively expanded with a combination of stimulating ligands. Methods and compositions for the administration of stimulatory ligands modified to self-insert into tumor cells, thereby stimulating an increase in the number of NK cells in proximity to a tumor, are also described. 138-. (canceled)39. A method of treating cancer comprising administering to a subject an effective amount of a composition comprising a membrane self-inserting peptide conjugated to an NK cell effector agent.4041-. (canceled)42. The method of claim 39 , wherein the composition comprises a membrane self-inserting peptide conjugated to IL-21.43. The method of claim 39 , wherein the composition comprises a membrane self-inserting peptide conjugated to 41BBL.44. The method of claim 39 , wherein the membrane self-inserting peptide is human Fc claim 39 , GPI claim 39 , transmembrane T cell receptor claim 39 , or pHLIP.4558-. (canceled)59. A method of expanding NK cells comprising administering to a cell population an effective amount of a composition comprising a membrane self-inserting peptide conjugated to an NK cell effector agent claim 39 , wherein the cell population comprises NK cells.6061-. (canceled)62. The method of claim 59 , wherein the composition comprises a membrane self-inserting peptide conjugated to IL-21.63. The method of claim 59 , wherein the composition comprises a membrane self-inserting peptide conjugated to 41BBL.64. The method of claim 59 , wherein the membrane self-inserting peptide is human Fc claim 59 , GPI claim 59 , transmembrane T cell receptor claim 59 , or pHLIP.65. The method of claim 59 , wherein administering to a cell population comprises administering the composition to a subject claim 59 , wherein the subject comprises the cell population.66. The method of claim 59 , wherein the composition comprises at least two ...

Composition for culturing regulatory t cells and use thereof

The present invention relates to a method for effectively proliferating regulatory T cells, by which, particularly, in the presence of a fusion protein dimer comprising IL-2 protein or a variant thereof and CD80 protein or a fragment thereof, CD4+, CD25+, and CD127− T cells can be effectively proliferated. In particular, when combined with a predetermined cell culture medium, regulatory T cells such as CD4+, CD25+, and CD127− can be effectively and specifically proliferated. In addition, when the method is used, it has been confirmed that the survival rate of regulatory T cells is remarkably increased as compared to a conventionally used culture method using IL-2, and a significant increase in the yield of Foxp3+ regulatory T cells has been confirmed. Thus, such a proliferation method can be used in the field of cell therapeutic agents using regulatory ‘I’ cells.

METHODS FOR ISOLATING HUMAN CARDIAC VENTRICULAR PROGENITOR CELLS

The present invention provides methods for isolating human cardiac ventricular progenitor cells (HVPs), wherein cultures of day 5-7 cardiac progenitor cells are negatively selected for one or more first markers expressed on human pluripotent stem cells, such as TRA-1-60, to thereby isolate HVPs. The methods can further include positive selection for expression of a second marker selected from the group consisting of JAG1, FZD4, LIFR, FGFR3 and TNFSF9. Large populations, including clonal populations, of isolated HVPs that are first marker negative/second marker positive are also provided. Methods of in vivo use of the HVPs for cardiac repair or to improve cardiac function are also provided. Methods of using the HVPs for cardiac toxicity screening of test compounds are also provided. 127.-. (canceled)28. A method for isolating a cell population comprising engraftable human cardiac ventricular progenitor cells (HVPs) , the method comprising:subjecting human pluripotent stem cells to activation of Wnt/β-catenin signaling on day 0, followed by inhibition of Wnt/β-catenin signaling from day 3 to day 5 to obtain a culture comprising HVPs positive for at least one surface marker selected from the group consisting of JAG1, FZD4, LIFR, FGFR3 and TNFSF9;on day 5-7, contacting the culture comprising HVPs with one or more first agents reactive with at least one first marker that is expressed on the surface of human pluripotent stem cells; andisolating first marker-nonreactive negative cells to thereby isolate a cell population comprising engraftable HVPs.29. The method of claim 28 , wherein the first marker is TRA-1-60.30. The method of claim 28 , wherein the at least one first marker is selected from the group consisting of TRA-1-60 claim 28 , TRA-1-81 claim 28 , TRA-2-54 claim 28 , SSEA1 claim 28 , SSEA3 claim 28 , SSEA4 claim 28 , CD9 claim 28 , CD24 claim 28 , E-cadherin claim 28 , Podocalyxin claim 28 , and combinations thereof.31. The method of claim 28 , wherein the first ...

GENERATING INDUCED NEURAL PROGENITOR CELLS FROM BLOOD

The present disclosure provides a method of generating induced neural progenitor cells from CD34+/CD45+ blood cells using a POU domain containing gene or protein and inhibitors of Smad and GSK-3β, without traversing the pluripotent state. Also provided are uses and assays of the cells produced by the methods of the disclosure. 1. A method of generating induced neural progenitor cells from CD34/CD45 blood cells comprising:{'sup': +', '+, 'a) providing CD34/CD45 blood cells that ectopically express, overexpress or are treated with a POU domain containing gene or protein and culturing said cells in media to allow expression of the POU domain containing gene or protein; and'}b) culturing the cells produced in (a) in basal neural progenitor media supplemented with inhibitors of Smad and GSK-3β to produce induced neural progenitor cells;wherein induced neural progenitor cells are generated without traversing the pluripotent state.2. The method of claim 1 , wherein the cells in (a) are cultured in hematopoietic stem cell culture media claim 1 , optionally for 2-4 days claim 1 , followed by reprogramming media claim 1 , optionally for 4-7 days.3. The method of claim 1 , wherein the method further comprises maintaining or expanding the cells produced in (b) in neural induction media.4. The method of claim 1 , wherein CD34/CD45 blood cells that ectopically express a POU domain containing gene or protein in (a) are produced by lentiviral transduction or are produced by providing an exogenous POU domain containing gene or protein.5. (canceled)6. The method of claim 1 , wherein the POU domain containing gene or protein is an Oct gene or protein claim 1 , wherein the Oct gene or protein is Oct-4 claim 1 , -2 claim 1 , -1 or -11.7. (canceled)8. The method of claim 6 , wherein the Oct gene or protein is Oct-4.9. The method of claim 1 , wherein the CD34/CD45 blood cells are derived from peripheral blood or umbilical cord blood.10. (canceled)11. (canceled)12. The method of claim 2 , ...

METHODS FOR ISOLATING HUMAN CARDIAC VENTRICULAR PROGENITOR CELLS

The present invention provides methods for isolating human cardiac ventricular progenitor cells (HVPs), wherein cultures of day 5-7 cardiac progenitor cells are negatively selected for one or more first markers expressed on human pluripotent stem cells, such as TRA-1-60, to thereby isolate HVPs. The methods can further include positive selection for expression of a second marker selected from the group consisting of JAG1, FZD4, LIFR, FGFR3 and TNFSF9. Large populations, including clonal populations, of isolated HVPs that are first marker negative/second marker positive are also provided. Methods of in vivo use of the HVPs for cardiac repair or to improve cardiac function are also provided. Methods of using the HVPs for cardiac toxicity screening of test compounds are also provided. 1. A method for isolating human cardiac ventricular progenitor cells , the method comprising:contacting a culture of day 5-7 cardiac progenitor cells comprising cardiac ventricular progenitor cells with one or more first agents reactive with at least one first marker that is expressed on human pluripotent stem cells; andseparating first marker-nonreactive negative cells from reactive cells to thereby isolate human cardiac ventricular progenitor cells.2. The method of claim 1 , wherein the at least one first marker is TRA-1-60.3. The method of claim 1 , wherein the at least one first marker is selected from the group consisting of TRA-1-60 claim 1 , TRA-1-81 claim 1 , TRA-2-54 claim 1 , SSEA1 claim 1 , SSEA3 claim 1 , SSEA4 claim 1 , CD9 claim 1 , CD24 claim 1 , OCT3 claim 1 , OCT4 claim 1 , NANOG claim 1 , SOX2 claim 1 , E-cadherin claim 1 , Podocalyxin claim 1 , alkaline phosphatase (AP) claim 1 , and combinations thereof.4. The method of claim 1 , wherein the culture is a day 6 culture of cardiac progenitor cells.5. The method of claim 1 , which further comprises:contacting the culture with one or more second agents reactive with at least one second marker that is a cell surface marker ...

Composition including Stem Cell-Derived Exosome for Inducing Adipogenic Differentiation and Adipose Tissue Regeneration

A composition for inducing differentiation into adipocytes or regenerating adipose tissues comprises, as an ingredient, exosomes derived from stem cells differentiating into adipocytes, or exosomes derived from proliferating stem cells. 1. A composition for inducing differentiation into adipocytes or regenerating adipose tissues comprising , as an ingredient , exosomes derived from stem cells differentiating into adipocytes.2. The composition of claim 1 , wherein the stem cells differentiating into the adipocyte comprise one or more of bone marrow stem cells claim 1 , cord blood stem cells claim 1 , and adipose-derived stem cells.3. The composition of claim 2 , wherein the stem cells differentiating into the adipocyte are human-derived claim 2 , animal-derived or plant-derived stem cells.4. The composition of claim 1 , wherein the exosomes are capable of inducing differentiation into adipocytes or regenerating adipose tissues from stem cells after treatment of the stem cells using the exosomes at a concentration of 1 to 150 μg per 1 mL of the composition.5. A cosmetic composition comprising the composition of .6. A medium composition for inducing differentiation into adipocytes comprising the composition of .7. An injectable preparation comprising the composition of and a hydrogel.8. A method of inducing stem cells differentiating into adipocytes claim 1 , the method comprising:preparing exosomes derived from the stem cells differentiating into adipocytes; andtreating stem cells with the exosomes for a time period.9. The method of claim 8 , further comprising:culturing the stem cells in a serum-free medium for a time period.10. The method of claim 8 , wherein the stem cells differentiating into the adipocyte comprise one or more of bone marrow stem cells claim 8 , cord blood stem cells claim 8 , and adipose-derived stem cells.11. The method of claim 10 , wherein the stem cells differentiating into the adipocyte are human-derived claim 10 , animal-derived or plant- ...

Novel peptides and combination of peptides and scaffolds for use in immunotherapy against renal cell carcinoma (rcc) 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.

GENOMIC ENGINEERING OF PLURIPOTENT CELLS

Provided are methods and compositions for obtaining genome-engineered iPSCs, and derivative cells with stable and functional genome editing at selected sites. Also provided are cell populations or clonal cell lines derived from genome-engineered iPSCs, which comprise targeted integration of one or more exogenous polynucleotides, and/or in/dels in one or more selected endogenous genes. 1. A cell or a population thereof , wherein (i) the cell is an induced pluripotent stem cell (iPSC) , a clonal iPSC , or an iPS cell line cell; and (ii) the cell comprises one or more exogenous polynucleotides at an endogenous T cell receptor (TCR) locus.2. The cell or population thereof of claim 1 , wherein the one or more exogenous polynucleotides is present in the constant region of the TCR locus.3. The cell or population thereof of claim 2 , wherein the TCR is knocked out.4. The cell or population thereof of claim 2 , wherein the one or more exogenous polynucleotides in the constant region of the TCR locus comprise a polynucleotide encoding a chimeric antigen receptor (CAR) claim 2 , and wherein the constant region of TCR locus is a TRAC locus.5. The cell or population thereof of claim 4 , wherein the CAR is expressed under the control of a TCR endogenous promoter.6. The cell or population thereof of claim 5 , wherein the CAR is expressed at about the same level as an endogenous TCR in a cell in which TCR is not knocked out.7. The cell or population thereof of claim 5 , wherein the CAR is expressed at about the same developmental stage as an endogenous TCR in a cell in which TCR is not knocked out.8. The cell or population thereof of claim 4 , wherein the CAR comprises a CD19 related CAR.9. The cell or population thereof of claim 4 , wherein the cell is an iPSC obtained from reprogramming a T cell to a pluripotent state (TiPSC) and genomically editing the TiPSC.10. The cell or population thereof of claim 4 , wherein the cell is an iPSC obtained from reprogramming a T cell ...

METHODS OF T CELL EXPANSION AND ACTIVATION

The present disclosure relates to methods, cells, and compositions for preparing T cell populations and compositions for adoptive cell therapy. In particular, provided herein are methods for efficiently expanding and activating T cell populations for genetic engineering and adoptive T cell immunotherapies. Also provided are cells and compositions produced by the methods and methods of their use. 1. A method of treating a disease in a subject in need thereof , the method comprising administering to the subject a therapeutically effective amount of an ex vivo cultured T cell population comprising activated human T cells prepared according to a method comprising:(a) reducing BAFF-R receptor activity in a population of T cells; and(b) culturing the T cells of (a) for about 3 to about 14 days in the presence of an anti-CD3 antibody, or a CD3-binding fragment thereof, and an anti-CD28 antibody, or a CD28-binding fragment thereof, under conditions appropriate for activating cytotoxic T cells, wherein the reducing and culturing activates and induces proliferation of activated T cells to yield activated T cells in sufficient numbers for use in therapy,wherein administering treats the disease in the subject, wherein the disease is selected from the group consisting of cancer and infection.2. The method of claim 1 , wherein the cancer is a blood malignancy.3. The method of claim 1 , wherein the blood malignancy is leukemia or lymphoma.4. The method of claim 1 , wherein the infection is selected from the group consisting of bacterial claim 1 , viral claim 1 , fungal claim 1 , and parasitic.5. The method of claim 1 , wherein the T cells are administered in a pharmaceutical composition.6. The method of claim 1 , wherein the T cells are administered by intravenous injection.7. The method of claim 1 , wherein the population of T cells prior to BAFF-R receptor reduction are selected from the group consisting of a leukocyte-containing cell mixture and a purified T cell population.8. ...

Method of Manufacturing Dual Specific T-Cells for Use in Cancer Immunotherapy

The present invention relates to autologous dual-specific lymphocytes, methods of making and uses for the treatment of tumors. In particular, the invention relates to methods producing autologous dual-specific lymphocytes comprising an endogenous receptor for at least one tumor associated antigen and an exogenous receptor for a strong antigen 1. A purified population of autologous dual-specific lymphocytes which have specificity for two or more antigens , wherein a population of lymphocytes is isolated from a patient and each lymphocyte expresses an endogenous receptor for a tumor associated antigen (TAA) and is genetically engineered to express an additional receptor for a strong antigen , wherein the population of dual-specific lymphocytes target a plurality of TAAs and the strong antigen.24.-. (canceled)5. The purified populations of claim 1 , wherein the strong antigen is a pathogen claim 1 , a pathogenic antigen claim 1 , or an alloantigen.6Listeria monocytogenes, Bacillus. The purified population of claim 5 , wherein the strong antigen is an antigen from a pathogen claim 5 , wherein the pathogen is selected from the group consisting of Calmette-Guérin claim 5 , tetanus claim 5 , diphtheria claim 5 , adenovirus claim 5 , herpes simplex virus claim 5 , vaccinia virus claim 5 , myxoma virus claim 5 , poliovirus claim 5 , vesicular stamatis virus claim 5 , measles virus claim 5 , influenza virus claim 5 , and Newcastle disease virus.710.-. (canceled)11. The composition comprising the purified population of dual-specific lymphocytes of and a pharmaceutically acceptable carrier.13. The method of claim 12 , wherein step (c) further comprises expanding the isolated tumor-specific lymphocytes in culture.14. The method of claim 12 , wherein step (a) further comprises isolating the lymphocytes from a tumor claim 12 , peripheral blood or bone marrow of the patient.15. The method of claim 12 , wherein the strong antigen is selected from the group consisting of a viral ...

Cell

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22. 145-. (canceled)46. A chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises a VH domain having the sequence shown as SEQ ID NO 24 , and a VL domain having the sequence shown as SEQ ID No. 26 or SEQ ID No. 40.4722. A CAR according to claim , wherein the CD19 binding domain comprises the sequence shown as SEQ ID No. 22 or SEQ ID No. 39.481. A cell comprising a CAR according to claim .491. A nucleic acid sequence encoding a CAR according to claim .504. A vector which comprises a nucleic acid sequence according to claim .51. A method for making a cell according to claim 48 , which comprises the step of introducing into a cell:a nucleic acid sequence encoding a CAR comprising a CD19-binding domain which comprises a VH domain having the sequence shown as SEQ ID No. 24, and a VL domain having the sequence shown as SEQ ID No. 26 or SEQ ID No. 40, ora vector comprising the nucleic acid sequence encoding the CAR.523. A pharmaceutical composition comprising a plurality of cells according to claim . The present invention relates to a cell which comprises more than one chimeric antigen receptor (CAR).A number of immunotherapeutic agents have been described for use in cancer treatment, including therapeutic monoclonal antibodies (mAbs), immunoconjugated mAbs, radioconjugated mAbs and bi-specific T-cell engagers.Typically these immunotherapeutic agents target a single antigen: for instance, Rituximab targets CD20; Myelotarg targets CD33; and Alemtuzumab targets CD52.The human CD19 antigen is a 95 kd transmembrane glycoprotein belonging to the immunoglobulin superfamily. CD19 is expressed very early in B-cell differentiation and is only lost at ...

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.

BUOYANCY ENABLED SEPARATION METHOD AND SYSTEM

A buoyancy enabled separation method for isolation from a sample including a variety of different cells a sparse subset of cells that is differentiated by a plurality of different cell surface markers. Microbubbles conjugated to antibodies are applied sequentially in a container with the previously used microbubbles disrupted prior to applying the next microbubbles conjugated to a different antibody. A system that includes a syringe-like container with a plunger and closeable opening. Further, a method for activating and expanding isolated T cells by applying antigen presenting microbubbbles having a flexible lipid shell mimicking an antigen presenting cell for generating immunological synapses. 1. A buoyancy enabled separation method for isolation from a sample including a variety of different cells a sparse subset of cells that is differentiated by a plurality of different cell surface markers , comprising:a) placing the sample in a container;b) adding first flexible shell microbubbles having a flexible shell with an inner bubble wall enclosing a gas and an outer bubble wall conjugated to a first antibody capable of binding to a first cell surface marker of a first subset of cells encompassed in the liquid sample;c) incubating over a time span sufficient to allow an interaction between the first antibody and the first cell surface marker binding the first antibody to the first cell surface marker;d) allowing the first microbubbles with the first subset of cells bound to the first microbubbles to separate by flotation from a remainder of the sample;e) removing waste from the container, including cells within the sample other than the first subset of cells;f) disrupting the first microbubbles such that the first set of isolated cells are no longer buoyant;g) adding second flexible shell microbubbles having a flexible shell with an inner bubble wall enclosing a gas and an outer bubble wall conjugated to a second antibody capable of binding to a second cell surface ...

Long lived engineered t cells for adoptive cell therapy

A method of generating an enriched population of T cells for use in adoptive immunotherapy applications includes isolating T-cells from a biological sample of a subject, and separating a population of CD4/CD8 T cells having a CD45RAintCD45ROint phenotype from the isolated T cells.