Abstract: Isolated nucleic acid molecules are provided which encode Fkhsf, as well as mutant forms thereof. Also provided are expression vectors suitable for expressing such nucleic acid molecules, and host cells containing such expression vectors. Also provided are pharmaceutical compounds and methods of identifying such compounds that can modulate the immune system. In addition are provided methods for identifying proteins regulated by Scurfin and proteins that induce or inhibit Foxp3 expression.

Abstract: An ex vivo method for generating a population of Treg capable of suppressing rejection of an organ or tissue transplant from a donor animal, comprises culturing CD4+ T cells from a recipient animal in the presence of IFN-? plus either donor specific or third-party antigen presenting cells, and harvesting a population of Treg capable of suppressing rejection in the recipient animal. The Treg can be administered, for example intravenously to the recipient, preferably immediately prior to the transplant to suppress transplant rejection. A similar strategy applicable to generating a population of Treg capable of suppressing an autoimmune condition in an animal wherein the animal mounts an immune reaction against an autoantigen, comprises culturing CD4+ T cells from the animal in the presence of cells presenting the autoantigen and IFN-? and harvesting a population of autoantigen reactive Treg.

Abstract: The present invention provides a method of detecting an immune response in a mammalian subject by (a) withdrawing blood or a blood fraction containing immune cells from the subject, (b) contacting the blood with an antibody that specifically binds to the cell surface HLA-F histocompatibility protein of activated mammalian immune cells and then (c) detecting the presence or absence of binding of immune cells to the antibody, wherein the presence of binding indicates the presence of an immune response in the subject.

Abstract: This invention is directed to the targeting of proteins or peptides of interest to an autophagosome, for their presentation on a major histocompatibility complex (MHC) class II molecule and methods of use thereof. Nucleic acids, vectors comprising the same, and compositions for targeting proteins or peptides of interest to an autophagosome, for their presentation on a major histocompatibility complex (MHC) class II molecule are disclosed as are methods of use thereof for stimulating or enhancing immune responses in a subject.

Abstract: The present invention relates generally to methods for stimulating T cells, and more particularly, to methods to eliminate undesired (e.g., autoreactive, alloreactive, pathogenic) subpopulations of T cells from a mixed population of T cells, thereby restoring the normal immune repertoire of said T cells. The present invention also relates to compositions of cells, including stimulated T cells having restored immune repertoire and uses thereof.

Abstract: Disclosed in this specification is a method to promote the growth of CD4+CD25Foxp3+ nTreg cells in a culture while treating with a PI-3K antagonist. The resulting cells are useful in the treatment of immune-related diseases.

Abstract: The present invention relates to the use of dendrimers with monophosphonic or bisphosphonic terminations in order to stimulate the growth of cell cultures or to activate cells in culture.

Abstract: Disclosed in this specification is a method to promote the growth of CD4+CD25Foxp3+ nTreg cells in a culture while treating the culture with a p70 S6 kinase inhibitor. The resulting cells are useful in the treatment of immune-related diseases.

Abstract: Disclosed in this specification is a method to promote the growth of CD4+CD25Foxp3+ nTreg cells in a culture while minimizing the production of IL-17. The resulting cells are useful in the treatment of immune-related diseases.

Abstract: Disclosed in this specification is a process for producing ex vivo expanded CD4+CD25+ regulatory T cells. The process includes the steps of extracting a sample that includes peripheral blood mononuclear cells from a human donor. The extracted cells include a certain number of cells which are CD4+CD25+ regulatory T cells. The relative population of the CD4+CD25+ regulatory T cells is enhanced such that the Treg cells constitute the majority of the cells in the sample. Thereafter, the population of the enriched Treg cells, that may include third-party derived Treg cells, is expanded to produce a clinically meaningful population of cells for use in the treatment of GVHD.

Abstract: The invention provides a technology which utilizes donor lymphocyte infusion and by which malignant tumor can be treated without causing such an adverse effect as graft versus host disease. Thus, a method for the treatment of malignant tumor is provided which comprises performing, in a patient requiring such treatment, donor lymphocyte infusion for the graft versus tumor reaction-based treatment of tumor and then performing radiation treatment, infusion of lymphocytes derived from the host or a third party identical in HLA type to the host, and intra bone marrow-bone marrow transplantation using bone marrow cells derived from the host or a third party identical in HLA type to the host, for the prevention and treatment of the graft versus host disease induced by the donor lymphocyte infusion.

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 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. The present invention relates to novel peptide sequences and their variants derived from HLA class I and class II molecules of human tumour cells which can be used in vaccine compositions for eliciting anti-tumour immune responses.

Abstract: The present invention is directed to the examination of the pattern of immunodominant T cell epitopes in the E6 protein of Human Papilloma virus and its further characterization in terms of its amino acid sequence and Human Leukocyte Antigen restriction. These epitopes are identified based on their ability to induce specific T cell responses and therefore, are important as sources of antigens for immunotherapies to treat cervical and other cancers. The present invention contemplates identifying a number of similar epitopes restricted by a wide variety of Human Leukocyte Antigen types so that they can be used together to develop preventative or therapeutic vaccines, which can be used for the general human population.

Abstract: The invention relates to stimulation of immune responses against antigen(s) and overcoming regulatory T cell suppression of such immune responses against antigen(s).

Abstract: Methods of stimulating or increasing differentiation to regulatory T cells, cultures of regulatory T cells and methods of reducing or decreasing an immune response, inflammation or an inflammatory response, among other things, are provided. Methods include, among other things, contacting blood cells or T cells with an amount of TGF-beta or a TGF-beta analogue and a retinoic acid receptor agonist, or an amount of a retinoid X receptor (RXR) or peroxisome proliferator activated receptor-gamma (PPARgamma) agonist, sufficient to stimulate or increase differentiation to regulatory T cells. Cultures of regulatory T cells include T cells that express a marker associated with regulatory T cells, such as cultures in which regulatory T cells represent, for example, 30% or more of the total number of cells in the culture.

Abstract: The invention involves the discovery that if dendritic cells loaded with a tumor antigen are cultured in interleukin-15 (IL-15), or if T cells activated by the dendritic cells are cultured in IL-15, Treg activity that is specific for the tumor antigen is reduced. This reduction in Treg activity results in an increase in anti-tumor immune response. Another embodiment of the invention involves the discovery that incubating dendritic cells with a MAP kinase inhibitor in combination with IL-15 gives synergistic benefits when the dendritic cells are used to activate T cells. Dendritic cell and T cell compositions incubated with IL-15 or a MAP kinase inhibitor are provided.

Abstract: Cytotoxic ?? T cells form an essential component in immunity to infections and tumors, and are also implicated in host defense against these challenges. The present disclosure demonstrates the ability of activated ?? T cells to cross-present exogenous antigens to CD8+ ?? T cells, a process previously thought to be mediated best by dendritic cells. In particular, the present disclosure provides a method for cross-presentation of antigen derived from tumor cell or microbial organisms such as viruses, bacteria, yeasts, parasites, and the like, or from cells infected with such organisms, to a CD8+ ?? T cell. Still further, the present disclosure provides a method for treatment of a tumor or a chronic or recurrent infectious disease, comprising delivering an antigen-presenting autologous ?? T cell population above into a patient requiring such treatment. Still yet further, a method is described for preparing a peptide-specific effector T cell.

Abstract: The present invention relates to expanded NK cells. The NK cells have been expanded ex vivo, are activated and have a cytotoxic phenotype. The cytotoxicity against malignant cells is markedly increased compared to non-expanded NK cells. The invention also relates to a method of treatment.

Abstract: The present invention discloses an immunotherapeutic method for treating patients suffering from colon cancer, by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more sentinel or metinel lymph nodes draining a tumour in the colon or a metastasis arising from a tumour in the colon. The present invention provides a new effective method for treating colon cancer and metastatic colon cancer, without adverse side effects associated with the known treatments.

Abstract: In order to target a diseased material in a subject, a monocyte, or monocyte-derived cell, such as a macrophage, which incorporates a magnetic material, such as a magnetic particle or a ferrofluid, preferably having a biocompatible coating, is proposed to be administered. A magnetic energy source may then be applied to the subject to destroy, rupture or inactivate the diseased material. Alternatively, the monocyte or monocyte derived cell may additionally include a therapeutic agent, which is thereby targeted at the diseased material.

Abstract: This invention relates to immunogenic compounds which may serve as ligands for NKT (natural killer T) cells and to methods of use thereof in modulating immune responses.

Abstract: Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing the involving a PD1 ligand.

Abstract: The invention generally relates to a composition comprising an enriched NK cell population. The invention further relates to a method of treating a solid tumor or a hyperproliferative disorder by administering the enriched NK cell population to a mammalian subject in need thereof.

Abstract: A method of expanding double negative T cells in culture is described. The method comprises (a) providing a starting sample comprising DN T cells or precursors thereof; (b) substantially depleting CD8+ and CD4+ T cells from the starting sample; (c) culturing the sample from step (b) with an immobilized T cell mitogen in a culture medium comprising an agent that can stimulate DN T cell growth; (d) washing the cells obtained in step (c) and resuspending in a culture medium comprising the agent without the T cell mitogen; and (e) washing the cells obtained in step (d) and resuspending in a culture medium comprising the agent and a soluble T cell mitogen. The DN T cells obtained by the method are useful in a variety of applications including the treatment of cancer, infectious diseases, graft versus host disease and autoimmune disease.

Abstract: This invention discloses immunostimulatory combinations of Tumor Necrosis Factor Receptor Superfamily (TN-FRSF) agonists, Toll-Like Receptor (TLR) agonists, “domain present in NAIP, CIITA, HET-E, TP-I (NACHT)-Leucine Rich Repeat (LRR)” or “NLR” agonists, RIG-I-Like Helicase or “RLH” agonists, purinergic receptor agonists and cytokine/chemokine receptor agonists, together with delivery methods. The combinations, when used alone at the site of pathology, provide immunostimulation that induces host humoral and cellular immunologic responses to eliminate pathogens or neoplasms. Alternatively, when the combinations are used with a defined antigens, these combinations can induce focused humoral and cellular immunologic responses useful as prophylactic and/or ameliorative therapeutic modalities for infections and the treatment of neoplastic disorders.

Abstract: A method whereby a cure is found for the Human Immunodeficiency Virus (HIV) by rebuilding and stimulating the infected individual's immune system.

Abstract: The present invention discloses an immunotherapeutic method for treating a patient suffering from a disseminated cancer by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more metastasis-draining lymph nodes (metinel nodes) draining a metastasis. The method comprises identification of one or more metinel lymph nodes in a patient, resection of the one or more nodes and, optionally all or part of the metastases, isolation of metastasis-reactive T-lymphocytes from said lymph nodes, in vitro expansion of said metastasis-reactive T-lymphocytes, and administration of the thus obtained T-lymphocytes to the patient, wherein the T-lymphocytes are CD4+ helper and/or CD8+ T-lymphocytes.

Abstract: Described are methods for isolating Hepatitis C Virus peptides (HPs) that have a binding capacity to a MHC/HLA molecule or a complex comprising the HCV-peptide and the MHC/HLA molecule. In one aspect, these methods include providing a pool of HCV-peptide, said pool containing HCV-peptides which bind to said MHC/HLA molecule and HCV-peptides which do not bind to said MHC/HLA molecule, contacting said MHC/HLA molecule with said pool of HCV-peptides whereby a HCV-peptide which has a binding capacity to said MHC/HLA molecule binds to said MHC/HLA molecule and a complex comprising said HCV-peptide and said MHC/HLA molecule is formed, detecting and optionally separating said complex from the HCV-peptide which do not bind to said MHC/HLA molecule and optionally isolating and characterizing the HCV-peptide from said complex. Also described are immunogenic compositions that stimulate a specific T cell response to hepatitis C virus when administered to a subject in an effective amount.

Abstract: Preparations comprising, especially, globin that is insoluble at neutral pH, and therefore at physiological pH, in which the globin has been obtained from whole blood by depigmentation in a medium that extracts or dissolves the haem but leaves the globin and the other constituents of proteinic nature in a substantially undissolved state, a process for the production of those preparations, and uses, especially for the filling, healing or regeneration of tissues, especially for chronic wounds and osseous healing or regeneration.

Abstract: The present invention discloses an immunotherapeutic method for treating a patient suffering from urinary bladder cancer by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more sentinel or metinel lymph nodes draining a tumour in the bladder or a metastasis arising from a tumour in the bladder The method provides a new effective method for treating urinary bladder cancer and metastatic bladder cancer, without adverse side effects associated with the known treatments.

Abstract: The invention is directed toward an improved formable bone composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing compound of demineralized lyophilized allograft bone particles ranging from about 100 to 850 microns. The bone particles are mixed in an excipient carrier combination containing carboxymethylcellulose, sodium hyaluronate, and a sodium phosphate saline buffer, the carboxymethylcellulose component of the carrier ranging from about 5.0 to about 11.0% of the composition and the sodium hyaluronate component of the carrier ranging from about 0.3 to about 0.7% of the composition, the composition having a pH between 6.5-7.5.

Abstract: The invention relates to a method of treating tumor cells within a patient wherein immature dendritic cells developed from the patient's monocyte cells and a lymphocyte cultured medium (LCM) adjuvant are introduced into the patient directly into the patient's tumor cells. The immature dendritic cells and LCM adjuvant combine with the antigens in the tumor cells to form a cancer vaccine, thereby immediately treating the tumor cells of the patient. The invention also provides a precursor treatment step of treating the patient with radiation therapy or a chemotherapy regimen.

Abstract: The invention provides a simple, cost-effective method of preparing a composition comprising natural killer (NK) cells useful for administering to a human. The method comprises (i) depleting CD3+ cells from a population of PBMCs comprising NK cells, and (ii) co-culturing cells from (i) with irradiated PBMCs that are autologous to the NK cells. Further provided by the invention are the compositions prepared thereby and methods of treating or preventing a disease or immunodeficiency in a host.

Abstract: The present invention relates to a T lymphocyte having an activity to induce a T lymphocyte recognizing an antigen and a technique to use the T lymphocyte.

Abstract: Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ.

Abstract: The present invention relates to systems and devices to treat and/or prevent inflammatory conditions within a subject and to related methods. More particularly, the invention relates to systems, devices, and related methods that sequester leukocytes and/or platelets and then inhibit their inflammatory action.

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

Abstract: An artificial bone marrow construct comprising a substrate having at least one well; a three dimensional biocompatible polymer matrix comprising a transparent polymer network containing microspherical voids, wherein the microspherical voids are each connected to at least one other void through inter-connecting pores; at least one LBL coating on a surface of at least one of the polymer network, voids and pores, a population of bone marrow cells comprising stem cells and stromal cells; and at least one bioactive agent. An artificial immune network comprising a polymer matrix with a population of immune cells comprising B-cells and T-cells is disclosed. Methods for testing the toxicity of drugs and other agents against bone marrow cells and methods for making universal blood using the artificial bone marrow constructs are also disclosed.

Abstract: An object of the present invention is to provide a technique to distinguish between Treg cells and activated T cells in a live state. Another object of the present invention is to provide a pharmaceutical composition for immunostimulation that can reduce the number of Treg cells in vivo and effectively express the immune response of activated T cells. In the method of the present invention, Treg cells are detected from test cells containing (i) regulatory T cells and (ii) at least one type of cell selected from the group consisting of naive T cells and activated T cells, wherein expressions of folate receptor 4 on the surfaces of cells are measured and Treg cells are detected using the expressions as an indicator. The present invention uses anti-folate receptor 4 antibody or folate receptor 4-binding fragment as an active ingredient contained in a pharmaceutical composition for immunostimulation.

Abstract: The present invention is directed to an isolated T-Cell Receptor constant domain and to peptides derived therefrom and recombinant constructs encoding same, effective in therapy of T cell mediated inflammatory disease, autoimmunity and graft rejection. Therapeutic and prophylactic vaccine compositions and methods utilizing these proteins and peptides, DNA vaccines encoding same and T cell vaccines thereof are further provided.

Abstract: The present invention provides methods and compositions for inhibition of Airway Hyperresponsiveness (“AHR”) by deleting, inactivating or inhibiting a subset of innate ?? T cells, alone or in conjunction with the inhibition of Natural Killer T (“NKT”) cells. The methods comprise selective leukophoresis to remove the ?? T cells from the individual's blood or administration of an agent that selectively targets and inhibits or inactivates the ?? T cells. The methods of the present invention can be used to treat AHR in a variety of different ailments, including allergen-induced conditions or respiratory conditions and diseases.

Abstract: Blocking the voltage-gated potassium channel Kv1.1 of T-cells causes the robust and exclusive production of TNF-?, and thus can be used for eradication of cancer, improved eradication of infectious organisms, increased permeability of blood vessels and the blood brain barriers to given molecules and cells, and improved neuronal features, regeneration function and development. Blocking the voltage-gated potassium channel Kv1.1 of T-cells causes the robust and exclusive production of TNF-?. Similarly, unblocking of a blocked Kv1.1 channel or opening of a Kv1.1 channel will prevent the T-cells from producing and secreting excess amounts of TNF-?, thus being useful in the treatment of conditions such as rheumatoid arthritis and for treating neurological diseases associated with defected functioning and/or pathological block of the Kv1.1 channel, among them PNH associated with Kv1 Abs; Encephalitis associated with Kv1 Abs; and Episodic-ataxia type 1 (EA-1), in all of which the T-cell blocked Kv1.

Abstract: Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

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

Abstract: The invention provides compositions and methods for cell separation. These reagents and techniques specifically agglutinate cells via surface antigen recognition and can be used to recover even rare cell types in high yield.

Abstract: A peptide consisting essentially of the amino acid sequence represented by SEQ ID NO:1; a peptide consisting essentially of the amino acid sequence represented by SEQ ID NO:2; or a mutant peptide consisting essentially of an amino acid sequence derived from the amino acid sequence represented by SEQ ID NO:1 or 2 by addition, deletion or substitution of one or more amino acids, the peptide being capable of forming a complex with an HLA-A2402 molecule to be recognized by HLA-A2402-restricted cytotoxic T lymphocytes or induce such lymphocytes. Such a peptide is useful as a cancer vaccine for epithelial cancer patients having HLA-A2402.

Abstract: A method is provided for inducing and enhancing neurogenesis and/or oligodendrogenesis from endogenous as well as from exogenously administered stem cells, which comprises administering to an individual in need a neuroprotective agent such as a nervous system (NS)-specific antigen, a peptide derived therefrom, T cells activated therewith, poly-YE, microglia activated by IFN-? and/or IL-4 and combinations thereof. The method includes stem cell therapy in combination with the neuroprotective agent.

Abstract: The invention relates to methods of expanding, stimulating or activating T cells by modulating the spatial organization of signal molecules presented to the T cells.

Abstract: A pharmaceutical composition comprises a therapeutic peptide or protein, a transport moiety capable of transporting said first peptide or protein into a hematopoietic cell differentiated from a common myeloid progenitor, and a linker between said first protein and said transport moiety, said linker susceptible to cleavage by an intracellular enzyme in the cell. A cell or collection of cells, e.g., platelets, containing such a composition is useful in methods for treating infection, inflammation, vascular injuries or any disorders involving or mediated by cells of the hematopoietic lineage. Methods of making such compostions are also disclosed.

Abstract: This invention provides a first polypeptide comprising all or a portion of the extracellular domain of ILT3, wherein the polypeptide is water-soluble and does not comprise the Fc portion of an immunoglobulin. This invention also provides a second polypeptide comprising (i) all or a portion of the extracellular domain of ILT3 operable affixed to (ii) the Fc portion of an immunoglobulin, wherein the Fc portion of the immunoglobulin comprises a function-enhancing mutation, and wherein the polypeptide is water-soluble. This invention further provides a third polypeptide comprising (i) all or a portion of the extracellular domain of ILT3 operable affixed to (ii) a transmembrane domain. This invention further provides related nucleic acids, expression vectors, host vector systems, compositions, and articles of manufacture and therapeutic and prophylactic methods using the polypeptides of the invention.