SBIR-STTR Award

Signaling in B cells resulting from the interaction of CD40 and its ligand, gp39, induces B cell activation, proliferation, differentiation (immunoglobulin production), and isotype switching. Functional studies have shown that treatment of mice with anti-gp39 antibodies blocks the interaction between CD40 on B cells and gp39 on T cells and inhibits antibody responses against thymus dependent antigens. Accumulating evidence in animal models indicates that anti-gp39 antibody administration prevents a variety of autoimmune processes, including autoantibody production, and interferes with allograft rejection. These results provide compelling evidence that antibodies to human gp39 may have significant therapeutic value in the management of autoimmune disease and the transplantation of allogeneic tissue and organs in humans. A murine monoclonal antibody specific for human gp39 is being developed for use in the treatment of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and diabetes. The murine anti-human gp39 antibody has been shown to functionally inactivate gp39 function in vitro and in vivo. The murine anti-gp39 antibody will be humanized by CDR-grafting of its variable region domains to reduce its potential immunogenicity and expressed using a high-level Chinese hamster ovary cell expression system.Proposed commercial application:The goal of this project is to develop a humanized antibody specific for human gp39 for use in the treatment of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, diabetes, and idiopathic thrombocytopenic purpura, and of graft-versus host-disease and graft rejection.National Institute of Allergy and Infectious Diseases (NIAID)

An antibody specific for human gp39 is being developed to use in the treatment of autoimmune diseases, such as systemic lupus erythematosis, idiopathic thrombocytopenia purpura, multiple sclerosis and rheumatoid arthritis. In addition, the anti-gp39 antibody may have significant therapeutic value in preventing rejection of transplanted tissues and organs. The interaction of gp39 with its receptor, CD40, has been shown to play a critical role in the regulation of humoral and cell-mediated immunity. Functional studies have demonstrated that the treatment of mice with anti- gp39 antibodies that block gp39-CD40 interaction inhibits antibody and cell-mediated immune responses against thymus dependent antigens. Compelling evidence in animal models indicates that anti-gp39 administration prevents a variety of autoimmune processes, including autoantibody production, and interferes with allograft rejection. A humanized anti-human gp39 antibody that blocks gp30-CD40 interaction has been generated. We propose to continue its in vitro and in vivo characterization and to develop a Chinese hamster ovary cell line transfectant capable of producing very high levels of the antibody. The characterization of the anti-gp39 antibody will be extended to preclinical models of autoimmune disease and allograft rejection in non-human primates.Proposed commercial application:The goal of this project is to develop a humanized antibody specific for human gp39 for use in the treatment of autoimmune disease, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, diabetes, and idiopathic thrombocytopenic purpura, and of graft-versus-host-disease and graft rejection.Thesaurus termsCD40 molecule, glycoprotein, hybrid antibody, immunosuppressive alloantiserum, immunosuppressive antileukocyte serum, monoclonal antibody antibody specificity, disease model, experimental allergic encephalomyelitis, method development, pharmacokinetics, species difference CHO cell, Callithricidae, Macaca fascicularis, SCID mouse, protein purification, transfectionNational Institute of Allergy and Infectious Diseases (NIAID)