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.