IMMUNOLOGICAL, BIOCHEMICAL, AND MOLECULAR STUDIES ON EPITHELIAL OVARIAN CANCER

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The main goals of this project are to generate data concerning the biology of epithelial ovarian cancer (EOC) with a special emphasis on the identification and characterization of antigens characteristic of this tumor type. On-going studies have identified four antigenic systems particularly pertinent to EOC: 1) MX35 antigen; 2) CA-125 antigen; 3) mucin antigens, e.g., MUC-1; and 4) blood group-related specificities, such as Lewis. This project will emphasize the detailed biochemical , immunochemical, and molecular analysis of these antigens. MX35 antigen has been identified as a glycoprotein of 95,000 dalton and CA-125 as a mucin- type molecule. One goal will be to clone the genes coding for the protein portion of these molecules, with the aim of understanding their molecular makeup and perhaps function. For mucin antigens, we plan to analyze in detail the glycosylation characteristics of MUC-1 mucin and CA-125 antigen. The goal is to determine how glycosylation contributes to the tumor-specific of antibodies directed towards these antigens and whether mucin glycosylation is a tissue-specific characteristic. The experiments could also point towards new targets for the immunotherapy of EOC. A final goal will be to determine whether peptide mimics of carbohydrate epitopes characteristic of EOC, e.g., Le/y, can serve as vaccines for the development of anti-tumor responses. Overall, the project aims at understanding the immunogenicity of ovarian cancer and using this information to develop new therapeutic approaches.