IMMUNOLOGY OF BLADDER TUMORS

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We are expanding our studies, so far supported by the National Bladder Tumor Task Force, in four directions. First, we shall try to obtain monoclonal antibodies to antigens associated with mouse bladder carcinoma. We shall prepare antibodies to cell surface antigens unique to individual carcinomas (if such can be identified), shared by bladder carcinomas but not other tumors, or present in many tumors but most strongly expressed in bladder carcinoma, and we shall analyze monoclonal antibodies to several different epitopes of each antigen. Second, we shall perform tumor localization studies in tumor-bearing mice by using monoclonal antibodies. Three already available monoclonal antibodies (and other ones to be raised) will be labelled and tested for ability to localize into growing tumors, so as to provide a model for similar work in man. Third, we shall use monoclonal antibodies for therapy of mouse bladder carcinoma. We shall assess the effect of monoclonal antibodies alone, as carriers of cytotoxic agents, and as modifiers of the local host anti-tumor response. Major effort will go into evaluation of a new model of immunotherapy using xenogeneic monoclonal antibodies to target a carrier-specific immune response against the tumor. We shall, also, develop methods to direct an anti-hapten immune response so that an anti-tumor reactivity is achieved, using hapten coupled monoclonal antibody in vivo. Finally, we shall raise anti-idiotypic antibodies to monoclonal antibodies specific for bladder tumor antigens and employ them in an attempt to induce active T cell-mediated and humoral immunity to bladder tumor antigens. Fourth, we shall make monoclonal antibodies to antigens of human bladder carcinoma. Attempts shall be made to obtain antibodies to antigens unique for one tumor, shared by all bladder carcinomas, and shared by bladder carcinomas and other tumors. We shall also test our panel of available monoclonal antibodies for reactivity with bladder carcinoma cells.