144 results about "Graft rejections" patented technology

Methods and compositions for inhibiting interleukin-21 (IL-21)/IL-21 receptor (MU-1) activity using antagonists of IL-21 or IL-21 receptor (“IL-21R” or “MU-1”), are disclosed. IL-21/IL-21R antagonists can be used to induce immune suppression in vivo, e.g., for treating, ameliorating or preventing autoimmune or inflammatory disorders, including, e.g., inflammatory bowel disease (IBD), rheumatoid arthritis (RA), transplant/graft rejection, psoriasis, asthma, fibrosis, and systemic lupus erythematosus (SLE).

Methods for modulating immune responses in a subject are provided. A preferred embodiment provides methods and compositions for reducing or inhibiting transplant rejection in a subject, preferably a human subject. Transplant rejection can be inhibited or reduced in a subject by administering an effective amount of B7-H4 polypeptide, fragments or fusions thereof to inhibit or reduce the biological activity of an immune cell or to reduce the amounts of proinflammatory molecules at a site of transplant. Th1, Th17 and Th22 cells are exemplary T cells that can be targeted for inhibition by B7-H4 polypeptides, fusion proteins or fragments thereof to inhibit or reduce inflammation.

The present invention provides novel purinones and purines useful for the prevention and treatment of autoimmune diseases, inflammatory disease, mast cell mediated disease and transplant rejection. The compounds are of the general formulae I and II:

The present invention provides methods and compositions for expanding Treg cells ex vivo or in vivo using one or more conjugates comprising a costimulatory moiety that stimulates at least one of three signals involved in Treg cell development and/or using dendritic cells pulsed with antigens and modified to display TGF-β, or hematopoetic stem cells or bone marrow cells modified to display TGF-β. The methods and compositions are useful, for example, in the treatment and prevention of autoimmune disease, including Type 1 diabetes and in preventing foreign graft rejection, as well as to establish mixed chimerism, induce tolerance to autoantigens, alloantigens or xenoantigens, beta cell regeneration, prevention of foreign graft rejection, and treatment of a genetically inherited hematopoietic disorder.

The invention relates to methods of evaluating transplant rejection in a host comprising determining a heightened magnitude of gene expression of genes in rejection-associated gene clusters. The disclosed gene clusters include genes that are substantially co-expressed with cytotoxic lymphocyte pro-apoptotic genes, cytoprotective genes and several other cytokine and immune cell genes.

The present invention provides methods and compositions for expanding T regulatory cells ex vivo or in vivo using one or more SAP agonists. The methods and compositions are useful in the treatment of autoimmune diseases and in preventing foreign graft rejection.

The present invention relates to a transplant rejection in an animal suppressed by administration of an antibody directed at a cell surface antigen selected from the group consisting of CD4, CD8, CD154, LFA-1, CD80, CD86 and ICAM-1, preferably an anti-CD4 antibody, together with a non-cellular protein antigen to generate in the animal a population of regulatory T-lymphocytes; reactivating said population of regulatory T-lymphocytes by further administration to the animal of the non-cellular protein antigen; and transplanting said organ or tissue whilst said population of regulatory T-lymphocytes is activated. Regulatory T cells can be generated ex vivo by culturing T cells with an antibody directed at a cell surface antigen selected from the group consisting of CD4, CD8, CD154, LFA-1, CD80, CD86 and ICAM-1, in the presence of cells that present either alloantigen or a non-cellular protein antigen. Ex vivo generated T-lymphocytes can be used as an alternative method of overcoming transplant rejection or in combination with the in vivo method. A similar approach can be adopted for the treatment of autoimmune conditions.

The present invention relates generally to the field of prophylaxis and therapy for inflammatory and/or fibrotic diseases which include responses to injuries. In particular, the present invention is related to agents that can bind or complex copper such as thiomolybdate, and to the use of these agents in the prevention and treatment of inflammatory and/or fibrotic diseases. Exemplary thiomolybdates include mono-, di-, tri- and tetrathiomolybdate; these agents are administered to patients to prevent and/or treat inflammatory and/or fibrotic diseases, such as pulmonary disease including pulmonary fibrosis and acute respiratory distress syndrome, liver disease including liver cirrhosis and hepatitis C, kidney disease including renal interstitial fibrosis, scleroderma, cystic fibrosis, pancreatic fibrosis, keloid, secondary fibrosis in the gastrointestinal tract, hypertrophic burn scars, myocardial fibrosis, Alzheimer's disease, retinal detachment inflammation and/or fibrosis resulting after surgery, and graft versus host and host versus graft rejections.

The present invention relates to methods and compositions for the reduction of xenotransplantation rejection. Specifically, the present invention relates, first, to transgenic cells, tissues, organs and animals containing transgenic nucleic acid molecules that direct the expression of gene products, including, but not limited to enzymes, capable of modifying, either directly or indirectly, cell surface carbohydrate epitopes such that the carbohydrate epitopes are no longer recognized by natural human antibodies or by the human cell-mediated immune response, thereby reducing the human immune system response elicited by the presence of such carbohydrate epitopes. In a preferred embodiment, the transgenic cells, tissues, organs and animals express nucleic acid molecules encoding functional recombinant alpha-Galactosidase A (alphaGalA) enzyme which modifies the carbohydrate epitope Galalpha(1,3)Gal. In a more preferred embodiment, the transgenic cells, tissues, organs and animals expressing the functional recombinant alphaGalA are transgenic pig cells, organs, tissues and/or animals. Second, the present invention relates to methods for xenotransplantation comprising introducing the transgenic cells, tissues and/or organs into human recipients so that a lower level of hyperacute rejection (HAR) is observed in the human recipients relative to the level of HAR observed in human recipients having received non-transgenic cells, tissues and/or organs.

The present invention relates to methods for delivery of fusion polypeptides into cells. Methods are provided for local delivery of fusion polypeptides, e.g., through the skin, eye and the airway, to prevent allergic inflammation, airway hyper-responsiveness and to block T cell activation. Methods for delivery of fusion polypeptides to suppress graft rejection are also provided.

A therapeutic composition or a vaccine comprising tumor membrane-anchored cytokines or other immunostimulatory or costimulatory molecules are provided. The therapeutic composition or a tumor vaccine can be used for treating a tumor or other disease such as autoimmune disorder, viral diseases, bacterial diseases, parasitic diseases, and transplant rejection.

Disclosed herein are materials and methods for modulating an immunologically adverse response to an exogenous or endogenous immunogen, including a cell, tissue, or organ associated immunogen. An implantable material comprising cells, such as but not limited to endothelial cells, anchored or embedded in a biocompatible matrix can modulate an adverse immune or inflammatory reaction to exogenous or endogenous immunogens, including response to non-syngeneic or syngeneic cells, tissues or organs, exogenous immunogens or stimuli, as well as ameliorate an autoimmune condition. The implantable material can be provided prior to, coincident with, or subsequent to occurrence of the immune response or inflammatory reaction. The implantable material can induce immunological acceptance in a transplant patient, reduce graft rejection and reduce donor antigen immunogenicity.

Improved indices for the diagnosis and evaluation of conditions affecting the eye. Specifically, the indices include an Enhanced Epithelial Irregularity Factor (eEIF) for the diagnosis and evaluation of conditions such as dry eye syndrome (DES), Bowman's Ectasia Index (BEI), including enhanced BEI (eBEI) and BEI-Max, and Bowman's Relative Thinning (BRT) Index for the diagnosis and evaluation of ectatic conditions such as keratoconus, pellucid marginal degeneration, post-refractive surgery ectasia, and keratoglobus, and Descemet's Membrane Thickening Index (DMT), Descemet's Rejection Index (DRI), and Descemet's Membrane Irregularity Factor (DIF) for the diagnosis and evaluation of conditions such as keratoplasty rejection and failure and Fuchs' dystrophy. These improved indices may be incorporated into optical coherence tomography systems, or any other imaging device capable of capturing high resolution images of the cornea, for more sensitive and specific diagnosis, treatment, and monitoring of certain corneal conditions, in addition to the evaluation of new treatments.

The invention relates to methods for modulating the immune function through targeting of CLIP molecules. The result is wide range of new therapeutic regimens for treating, inhibiting the development of, or otherwise dealing with, a multitude of illnesses and conditions, including autoimmune disease, cancer, Alzheimer's disease, allergic disease, transplant and cell graft rejection, HIV infection and other viral, bacterial, and parasitic infection, and AIDS. Methods are also provided for preparing a peptide having the property of being able to displace CLIP by feeding one or more peptide sequences into software that predicts MHC Class II binding regions in an antigen sequence and related products.

A pharmaceutical combination comprising an accelerated lymphocyte homing agent in free form or in pharmaceutically acceptable salt form, and one or more compounds selected from the group consisting of an antibody to the IL-2 receptor, an immunosuppressive macrocyclic lactone and a soluble human complement inhibitor is used to treat or prevent insulin-producing cell graft rejection.

A chimeric protein compound for durable and efficient suppression to different chemotactic factor receptors, its nucleic acid sequence, and the process for preparing and testing its products are disclosed. It can be used to prevent and cure HIV infection, tumor transfer, tissue transplant rejection and self immunopathy. Its advantages are high durability, broad spectrum, and high selectivity.

The invention relates to an application of PD-L1 gene modified bone marrow mesenchymal stem cells in graft rejection. According to the invention, immune state can be regulated and graft rejection can be inhibited, significant guidance in clinical application of xenogeneic organ transplantation is provided, foundation for inducing peripheral immune tolerance is established, and application prospect is broad.

The present invention provides substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments thereof and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments thereof. The antibodies, fusion proteins or fragments are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Amino acid substitutions, particularly substitution of an aspartate residue at Kabat position 101 of CDR3 VH (CDRH3), result in improved therapeutic properties, such as decreased dissociation rates, improved CDC activity, improved apoptosis, improved B-cell depletion and improved therapeutic efficacy at very low dosages. Veltuzumab, a humanized anti-CD20 antibody that incorporates such sequence variations, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, allowing therapeutic effect at dosages as low as 200 mg or less, more preferably 100 mg or less, more preferably 80 mg or less, more preferably 50 mg or less, most preferably 30 mg or less of naked antibody when administered i.v. or s.c.

The present invention relates specific activation of a regulatory T cell via a specific CD4 epitope and uses thereof, e.g. for the treatment of an autoimmune disease or an allergy or asthma or graft rejection or tolerance induction.

Disclosed is a method of inhibiting acute and chronic tissue transplant rejection in a subject with a tissue transplant. The method comprises the step of administering to the subject an effective amount of a compound represented by Formula (I):

The values of the variables in Formula (I) are described herein.

The invention describes new peptides containing epitopes recognized by CD4+ natural killer T (NKT) cells for increasing activity for use in infectious diseases, autoimmune diseases, immune reaction to administration of allofactors, allergic diseases, therapy of tumors, prevention of graft rejection and prevention of immunization against viral proteins used in gene therapy or gene vaccination.

An antigen-specific T-cell response to alloantigen, tissue-specific antigen (e.g., islet antigen or other autoantigens involved in autoimmune disease), or self (or host) antigen is detected at an early stage of graft rejection or recurrent autoimmunity. An increase in cytotoxic lymphocyte gene (CLG) expression in peripheral blood is a risk factor for development of deleterious immune responses, which may be confirmed by functional assays. For example, the distinction between production of regulatory or inflammatory cytokines by T cells may dissect the type of immune response which is being induced: the survival of transplanted islet cells used to treat type 1 diabetes may be monitored, loss of the transplant by graft rejection (i.e., an alloantigen target) may be distinguished from autoimmune disease (i.e., a self or host antigen target).