Abstract: The present invention is directed to a method of generating antigen specific T cells. Furthermore, the invention is directed to antigen specific T cells, isolated transgenic TCR's, pharmaceutical compositions containing same and their use in adoptive cell therapy. This invention in particular pertains to the use of cells co-expressing allogeneic MHC molecules and antigens to induce peptide-specific T cells from non-selected allogeneic T cell repertoires.

Abstract: The arming of activated T cells (ATC) with BiAbs can overcome major barriers for successful adoptive immunotherapy. The BiAb approach takes the advantage of the targeting specificity of monoclonal antibodies and the cytotoxic capacity of T cells to lyse tumors. Arming of ATC with BiAb makes every T cell an antigen-specific CTL and infusions of such cells will markedly increase the effective precursor frequency of CTL in the cancer patient. Furthermore, the ability of such armed ATC to kill multiple times without rearming with BiAb, secrete tumoricidal cytokines, secrete chemokines, and survive in patients for up to 8 days after the last infusion or in Beige/SCID mice for over 13 weeks after cessation of treatment. The persistence of cells in the Beige/SCID after infusion show long-term survival capability in the host.

Abstract: A method for treating latent HIV infection is disclosed. The method includes administering to a subject in need of such treatment an effective amount of an anti-I?B? agent, an anti-I?B? agent or both; and administering to the subject an effective amount of an antiviral agent. A pharmaceutical composition for treating latent HIV infection is also disclosed.

Abstract: The present invention provides CTL epitope peptides and polyepitope peptides from 14 distinct antigens of human cytomegalovirus (HCMV) that are restricted through HLA the must commonly prevalent class I alleles in different ethnic populations of the world. These epitopes provide an important platform for CTL epitope-based vaccines against HCMV. The present invention further provides vaccine compositions comprising the subject epitope and polyepitope peptides and methods for vaccination of humans and for the adoptive transfer of HCMV-specific T cells to human subjects. The present invention further provides reagents and methods for determining the HCMV status or level of HCMV-specific immunity of a subject.

Abstract: The present invention relates to a composition, method and kit for treating cancer. The treatment comprises administering a pre-sensitizing agent to a tumor or subject, and administering a cancer therapy to the tumor cells or subject. The pre-sensitizing agent increases or induces the apoptosis of the tumor cells, as compared to the rate of apoptosis of tumor cells that have not been pre-sensitized prior to receiving the cancer therapy. In another aspect, the invention relates to a kit comprising a pre-sensitizing agent and a cancer therapy.

Abstract: The present invention relates to a method for producing adaptive regulatory T cells from effector T cells by contacting the effector T cells with retinoic acid. Adaptive regulatory T cells produced by this method are Foxp3+, home to the gut, and are refractory to reversion in vivo. As such, such cells find application in the treatment of autoimmune disease and facilitating transplantation tolerance.

Abstract: This invention relates to therapeutic compositions comprising a surface active copolymer, such as poloxamer-188, in an amount effective to enhance microvascular blood flow and/or inflammation in injured skin or other tissue, and methods of using the therapeutic compositions of the invention to inhibit decreased blood flow associated with an injury, disease, or disorder.

Abstract: This invention provides novel carbonic anhydrase (CAIX) nucleic acid and peptide sequences, as well as related methods and compositions, including anti-cancer immunogenic agent(s) (e.g. vaccines and chimeric molecules) that elicit an immune response specifically directed against cancer cells expressing a CAIX antigenic marker. The novel CAIX variant and related compositions are useful in a wide variety of treatment modalities including, but not limited to protein vaccination, DNA vaccination, and adoptive immunotherapy.

Abstract: Provided are cells expressing HCV epitope-reactive recombinant T cell receptors useful in the treatment and/or prevention of acute or chronic HCV and HCV-related conditions or malignancies. The invention further provides methods of preparing HCV epitope-reactive T cell receptors and methods of treatment using cells expressing HCV epitope-reactive recombinant T cell receptors. Polynucleotides, constructs and vectors encoding HCV epitope-reactive recombinant T cell receptors are also provided.

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

Abstract: This invention provides a method of treating cancer or infection by administering T cells transfected with T cell receptors (TCRs) which in their soluble form have a half life for their interaction with their cognate peptide-MHC complex chosen to enhance the avidity of the T cells for target cells presenting that peptide MHC complex while maintaining the activation specificity of the T cells by that peptide-MHC complex.

Abstract: 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.

Abstract: Methods are disclosed herein for specifically inducing proliferation of CD4+ T cells. The methods are of use in treating immunodeficiencies, such as an immunodeficiency produced by infection with an immunodeficiency virus, such as infection with a human immunodeficiency virus (HIV). The methods include contacting isolated mammalian CD4+ T cells with an effective amount of a thymic stromal derived lymphopoietin (TSLP) polypeptide or a therapeutically effective amount of nucleic acid encoding the TSLP polypeptide, thereby inducing proliferation of the T cells. Methods are also disclosed for treating an IgE mediated disorder, such as asthma. The methods include administering to a subject a therapeutically effective amount of a TSLP antagonist. Transgenic mice are also disclosed herein.

Abstract: This invention is directed to therapeutic compositions containing non-MHC-restricted T-cells/NK-cells in combination with MHC-restricted T-cells and especially to therapeutic compositions, which comprise LAK cells. Furthermore, the present invention is directed to the use of the above combination in the treatment of tumors in humans, which tumors show a missing, low or aberrant expression of MHC class 1a or 1b molecules. By using the aforementioned compositions/combinations it is possible to provide a balanced selective pressure against emergence of tumor cell variants that would otherwise escape immune detection.

Abstract: A redirected Treg cell is endowed with specificity toward a selected target antigen or ligand. The cell contains a chimeric receptor polypeptide that is expressed in a single, continuous chain, with an extracellular recognition region displayed on the surface of the cell, a transmembrane region and an intracellular signaling region. The extracellular recognition region is specific for the selected target antigen or ligand. The intracellular signaling region includes a combination of T-cell signaling polypeptide moieties, which combination, upon binding of the extracellular recognition region to the selected target antigen or ligand, triggers activation of the redirected Treg cells to cause suppression of T-cell mediated immunity. Such redirected Treg cells may be used to suppress undesired activity of T effector cells thereby mediating an immune or inflammatory response.

Abstract: An immunogen includes an isolated peptide of 800 amino acid residues or fewer having the amino sequence ILSAFSVYV (SEQ ID NO:1) with four or fewer amino acid substitutions, a superagonist variant of SEQ ID NO:1, or an amino acid sequence having the formula: (I/K/T/V/M)-L-(S/L)-(A/E/N/D/Q)-(F/V)-(S/M/V/I)-(V/D/R/G/H)-Y-(V/I/L) (SEQ ID NO:13). The immunogens can be used in compositions and in the treatment of disorders.

Abstract: Methods are provided for suppressing the immune system response in recipients of transplanted organs, tissues or cells. An extracorporeal quantity of blood from the intended transplant recipient is treated to induce monocytes contained in the blood to differentiate and form dendritic cells. The maturation of the dendritic cells is truncated at a stage where the dendritic cells can inactivate T cell clones which would otherwise generate an undesired immune system response. The immature dendritic cells can be directly administered to the transplant recipient, or the dendritic cells can be co-incubated with the bone marrow or stem cell preparation, prior to transplantation, in order to suppress or eliminate anti-recipient donor T cells contaminating the bone marrow or stem cell preparation. The methods can be used to suppress graft versus host disease in recipients of transplanted bone marrow or stem cells, or to suppress rejection of transplanted organs or tissue.

Abstract: Methods are disclosed for the generation of immunosuppressive regulatory T cells. The methods can include contacting a population of CD4+CD25? T cells with a T cell receptor (TCR)/CD3 activator, a TCR co-stimulator activator, and rapamycin. Kits for the generation of immunosuppressive regulatory T cells, methods of use, and cell populations are also disclosed.

Abstract: DKK1 compositions comprising a DKK1 protein, DKK1 peptide, DKK1 DNA, DKK1-specific CTLs and Th1 cells and associated methods for treating cancer and cancer-mediated disorders in a human or animal subject in need of such treatment by administering a DKK1 composition to prevent or treat cancer are disclosed herein. The DKK1 compositions can be used alone, or in combination with other treatments, for the treatment of various cancers including ovarian, breast, colonic, brain, lung, prostate, pancreatic, lymphoma, esophageal carcinomas and melanoma.

Abstract: The present invention provides an NKT cell stimulating agent containing antigen-presenting cells pulsed with an NKT cell ligand, to be administered submucosally in the upper airway. By submucosal administration in the upper airway, it is possible to stimulate NKT cells and stimulate immune reactions extremely efficiently with a small number of NKT cell ligand-pulsed antigen-presenting cells. By submucosal administration in the upper airway, NKT cells can be induced selectively in cervical lymph nodes.

Abstract: Compositions and methods for the therapy and diagnosis of immune-mediated inflammatory diseases, including inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis, are disclosed. Illustrative compositions comprise one or more bacterial polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention or treatment of immune-mediated inflammatory disease.

Abstract: Methods for inducing antigen-specific T cell tolerance are disclosed. The methods involve contacting a T cell with: 1) a cell which presents antigen to the T cell, wherein a ligand on the cell interacts with a receptor on the surface of the T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor on the surface of the T cell which inhibits interaction of the ligand on the antigen presenting cell with the receptor on the T cell. In a preferred embodiment, the cell which presents antigen to the T cell is a B cell and the receptor on the surface of the T cell which mediates contact-dependent helper effector function is gp39. Preferably, the antagonist is an anti-gp39 antibody or a soluble gp39 ligand (e.g., soluble CD40). The methods of the invention can be used to induce T cell tolerance to a soluble antigen or to an allogeneic cell.

Abstract: The invention provides methods for producing an autoantigen-specific regulatory T cell enriched composition, and resultant compositions and methods of use.

Abstract: This document relates to compositions and methods for modulating an immune response. For example, compositions of immunostimulatory CpG oligonucleotides derived from retroviral genomes are provided.

Abstract: Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

Abstract: Methods and materials to modulate the immune response to treat or prevent a disease or to prevent transplant rejection, including methods of making T helper-antigen presenting cells and/or T regulatory-antigen specific cells and methods of using these cells. The invention also relates to methods of making exosome-absorbed dendritic cells and the uses of these cells to modulate the immune response to treat or prevent a disease or to prevent transplant rejection.

Abstract: Described herein is an activated synovial autoreactive T cell and compositions thereof. Methods or preparing T cell compositions that may be used for treating rheumatoid arthritis are also described.

Abstract: Compositions and methods are provided for preventing or treating neoplastic disease in a mammalian subject. A composition is provided which comprises an enriched immune cell population reactive to a human endogenous retrovirus type E antigen on a tumor cell. A method of treating a neoplastic disease in a mammalian subject is provided which comprises administering to a mammalian subject a composition comprising an enriched immune cell population reactive to a human endogenous retrovirus type E antigen, in an amount effective to reduce or eliminate the neoplastic disease or to prevent its occurrence or recurrence.

Abstract: The present invention relates to a method of inhibiting antigen-dependent proliferation of T-cells in a subject without substantially inhibiting mitogen-dependent proliferation of T-cells in the subject. The method includes administering to the subject an effective amount of a polyunsaturated fatty acid, or a salt or derivative of a polyunsaturated fatty acid.

Abstract: The invention provides a method for inhibiting proliferation of cancer cells, as well as methods for detecting and treating various cancers, including cancer of the ovary, breast, prostate and colon. The method comprises contacting a cancer cell with an IGF-related molecule of the invention or administering an IGF-related vaccine to the cancer patient. In one embodiment, the molecule is an immunogenic peptide derived from IGFBP-2 or from IGF1 R. The invention additionally provides methods for detecting and treating cancer using IGF-related molecules.

Abstract: Adoptive immune cells obtained by a method including (a) obtaining mammalian antigen-presenting associated cells; (b) culturing the resulting cells from step (a) in a culture liquid contained in a culture vessel coated with a sugar chain-containing polymer; and (c) detaching the cells from step (b) by shaking the culture vessel without treating the cells with an enzyme and without using a cell detaching tool. A method for treating a malignant tumor, type I diabetes, an atopic allergic disease or an infection, by administering the adoptive immune cells to a patient. A pharmaceutical composition for treating a malignant tumor, type I diabetes, an atopic allergic disease or an infection, including the adoptive immune cells and a pharmaceutically acceptable carrier.

Abstract: Compositions for platelet rich plasma (PRP) are provided. Generally, these compositions comprise a higher concentration of platelets and white blood cells than whole blood. The concentrations of the platelets and/or the white blood cells may be two to eight times the respective concentrations in whole blood. These compositions may have depressed concentrations of red blood cells and hemoglobin. In some variations, the compositions may be useful to treat damaged connective tissue and/or to slow or stop cardiac apoptosis after a heart attack. The PRP composition may be delivered in conjunction with reperfusion therapy.

Abstract: The present invention relates to improved autologous T cell vaccines and improved methods for their production. The invention is also directed to methods for treating autoimmune diseases such as multiple sclerosis or rheumatoid arthritis using autologous T cell vaccines. The invention is further directed to the diagnosis of T cell associated diseases.

Abstract: A method for treating multiple myeloma in a subject by administering 17-allylamino-17-demethoxy-geldanamycin or 17-amino geldanamycin, or a prodrug of either 17-AAG or 17-AG, to the subject.

Abstract: The present invention provides novel isolated and purified polynucleotides and polypeptides related to a novel ligand for glucocorticoid-induced TNF receptor (GITR). The invention also provides antibodies to the GITR ligand (GITRL). The present invention also is directed to novel methods for diagnosing, prognosing, monitoring the progress of, and treating disorders arising from disregulation of the immune system (e.g., autoimmune disorders, inflammatory diseases, and transplant rejection, and cancers and infectious diseases) using GITRL and/or modulators of GITRL. The present invention is further directed to novel therapeutics and therapeutic targets and to methods of screening and assessing test compounds for the intervention (treatment) and prevention of said disorders arising from disregulation of the immune system, as related to GITRL and GITR.

Abstract: Disappearance of a cell population, designated CD4+ CD44v.low, has been shown to be associated with cachexia and lymphopenia, and those conditions can be treated or delayed by administering those cells to a patient. In addition, disclosed are assays for those cells for diagnosing or prognosticating cachexia and/or lymphopenia and the end of the honeymoon period in Type I diabetes. Furthermore, disclosed herein are methods related to the use of CD4+ CD44v.low cells in promoting insulin-secreting beta cell mass.

Abstract: A method for preparing a T cell population, wherein the T cell population expresses CD45RA and expresses at least one selected from the group consisting of CD62L, CCR7, CD27, and CD28, characterized in that the method comprises the step of culturing a cell population comprising a T cell, in the presence of fibronectin, a fragment thereof or a mixture thereof.

Abstract: Methods are disclosed for the generation of immunosuppressive regulatory T cells. The methods can include contacting a population of CD4+CD25? T cells with a T cell receptor (TCR)/CD3 activator, a TCR co-stimulator activator, and rapamycin. Kits for the generation of immunosuppressive regulatory T cells, methods of use, and cell populations are also disclosed.

Abstract: Provided is a composition for in vivo transplantation for the treatment of human cervical cancer, comprising mononuclear cells derived from umbilical cord blood and a pharmaceutically acceptable carrier. When the umbilical cord blood-derived mononuclear cells are transplanted in vivo, cervical cancer can be effectively treated. In particular, the mononuclear cells derived from the umbilical cord blood retain high differentiation and proliferation abilities and exhibit very low graft-versus-host (GVH) reactions which are side effects caused by transplantation, and thus, can be transplanted to many patients.

Abstract: A novel compound of the formula (1): wherein X is a tyrosine residue or a methionine residue; Y and Z each are a single bond or the like; R1 is a hydrogen atom or the like; R2 is a hydroxy group or the like; R3 is a hydrogen atom, alkyl group, amino group or the like; R4 is a hydrogen atom, alkyl group, carboxy group or the like; m is 1 or 2; and n is an integer of 0 to 2, with the proviso that when n is 0, R3 is a hydrogen atom or an alkyl group, or a pharmaceutically acceptable salt thereof, and its use in cancer immunotherapy.

Abstract: The present invention relates to an antibody fusion protein which specifically recognizes the VA, HN or F surface antigen of the New Castle Disease Virus (NDV), a surface molecule of a tumor-unspecific T cell or a surface molecule of a dendritic cell and an immunocytokine. Also encompassed by the present invention are polynucleotides encoding the aforementioned antibody fusion protein as well as tumor-unspecific key cells or dendritic cells bound by the antibody fusion protein. Moreover, the present invention relates to a method of treating a tumor in a subject comprising administering to the said subject the antibody fusion protein, the tumor-unspecific T cell, the dendritic cell or the polynucleotide of the invention. Preferably, the said tumor is a solid tumor.

Abstract: The present invention is directed to a T cell receptor (TCR) recognizing antigenic peptides derived from tumor-associated antigen FMNL1/KW13 and being capable of inducing peptide specific killing of a target cell. The present invention is further directed to one antigenic peptides derived from tumor-associated antigen FMNL1/KW13, to an antigen specific T cell, comprising said TCR, to a nucleic acid coding for said TCR and to the use of the antigen specific T cells for the manufacture of a medicament for the treatment of malignancies characterized by overexpression of FMNL1/KW13.

Abstract: It is disclosed herein that Brachyury is expressed in human tumors, specifically in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testes, as well as in lung, colon and prostate carcinomas. Immunogenic Brachyury polypeptides are disclosed herein. These polypeptides can be used in diagnostic assays for Brachyury expression, as well as for inducing an immune response to Brachyury. Polynucleotides encoding the immunogenic Brachyury polypeptides, vectors including these polypeptides, host cells transformed with these vectors, and methods of using these polypeptides, polynucleotides, vectors, and host cells are provided. Methods of diagnosing a Brachyury-expressing cancer are also provided. Exemplary cancers include lung, colon, small intestine, stomach, kidney, bladder, uterus, ovary, and testes and prostate cancers. Methods of treating cancer are also disclosed.

Abstract: This invention provides a cell presenting at least one T cell receptor (TCR) anchored to the membrane by a transmembrane sequence, said TCR comprising an interchain disulfide bond between extracellular constant domain residues which is not present in native TCRs.

Abstract: The present invention provides a cellular vaccine for therapeutic or prophylactic treatment of a pathological condition, the vaccine comprising or consisting of a population of CD 4+ T cells modified such that they contain an antigenic component, and/or a nucleic acid molecule encoding an antigenic component thereof, wherein the T cells are (a) activated, or capable of being activated, and (b) apoptotic, or capable or being made apoptotic. The invention further provides an adjuvant composition for use in a method of vaccination, the composition comprising or consisting of a population of T cells, wherein the T cells are (a) activated, or capable of being activated, and (b) apoptotic, or capable or being made apoptotic.

Abstract: We demonstrate herein that neuritin controls the homeostasis of regulatory T cells in an antigen dependent manner. Based on this discovery, we describe herein the application of neuritin as a therapeutic agent to manipulate antigen specific regulatory T cells in various disease settings is described. Thus manipulation of Treg cells and DCs through neuritin can be used to enhance immunotherapy of autoimmune diseases, cancer and infectious diseases, as well as enhance lymphocyte engraftment in settings of donor lymphocyte infusion, bone marrow transplant, as well as other types of transplants, and adoptive transfer.

Abstract: The present invention relates to immunotherapeutic methods, and molecules 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-helper cell peptide epitopes, alone or in combination with other tumour-associated peptides, that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumour immune responses. In particular, the present invention relates to 49 novel peptide sequences derived from HLA class II molecules of human tumour cell lines which can be used in vaccine compositions for eliciting anti-tumour immune responses.

Abstract: The invention features a method for expanding and engrafting nucleated cells, e.g., progenitor cells, such as hematopoietic cells, obtained from cord blood by co-culturing the nucleated cells with adherent stroma cells, e.g., mesenchymal stem/progenitor cells, also obtained from cord blood.

Abstract: Methods and compositions are provided for inducing neovascularization in injured tissues with endothelial progenitor cells (EPCs). Mixtures of purified CD34+ endothelial progenitors and purified CD14+ monocytes, or products of an in vitro co-culture of purified CD34+ endothelial progenitor cells and purified CD14+ monocytes provide neovascularization after administration to a subject having a tissue injury, such as an ischemic injury.

Abstract: An artificial antigen presenting system is presented. The herein presented microspheres combine negative regulators individually or at varying combinations along with MCH molecules and can induce antigen specific tolerance. The herein described methods provide for the construction of artificial biodegradable microsomes containing MHC: peptide complexes, accessory molecules, co-stimulatory molecules, adhesion molecules, and other molecules relevant to T cell binding or modulation. Additionally, the present invention is directed to compositions and methods for treating conditions which would benefit from modulation of T cell response, for example, autoimmune disorders, allergies, cancers, viral infections, and graft rejection.