BLADDER CANCER TUMOR ASSOCIATED ANTIGENS

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Serologic and cytotoxic evidence for the existence of bladder cancer tumor associated antigens have been reported. However, the distribution of these antigens and their clinical relevance remains to be defined. The objectives of this proposal are to accurately define the existence, distribution, and clinical relevance of tumor associated antigens on bladder cancer cells. This will be accomplished using the following methods: 1. New bladder carcinoma cell lines will be established in tissue culture. These cell lines will serve as a continual source of antigen for subsequent analysis. 2. Autologous combinations of patient's sera and tumor cells in tissue culture will be tested using the immune adherence and protein A assays to determine the presence of autologous reactivity to cell surface tumor associated antigens. Autologous testing eliminates reactivity caused by allogantigens and permits identification of antigens unique for an individual tumor. High titer sera will be further analyzed with serologic absorption using a wide variety of normal and malignant cell lines to define the distribution of the reactivity. Correlation between the presence of autologous antibody and the patient's clinical course will be assessed to evaluate whether the presence of antibody to autologous tumor alters the patient's prognosis. 3. Murine monoclonal antibodies will be produced to bladder tumor associated antigens using new and previously established bladder cancer cell lines. Serologic characterization with the mixed hemadsorption assay will be used to define the distribution of reactivity of the monoclonal antibodies on cultured cells. In addition, testing will be performed on formalin fixed and frozen tissue sections using an immunoperoxidase assay. Monoclonal antibodies with limited distribution will be used to defined subsets of human bladder cancer. Tumors defined by cell surface antigen phenotype will then be correlated with the clinical course of patient's bearing these neoplasms to determine if functionally different tumors, ie., neoplasms with different prognoses, can be identified.