Monoclonal antibody F36/22 (IgG3, recognizes a glycoprotein with Mr of 700- 1000k) has been shown immunohistochemically to be reactive with all human common epithelial ovarian cancers, while normal ovary expresses no detectable level of immunostain. Human exfoliated ovarian tumor cells are usually disseminating throughtout the entire peritoneal cavity, and represent an ideal target for therapeutic manipulation in a confined compartment. A recently available human ovarian carcinoma xenograft in female athymic mice, NIH:OVCAR-3, expresses antigen recognized by monoclonal antibody F36/22 and resembles the human disease by producing ascites and intra-abdominal carcinomatosis. Using monoclonal antibody F36/22 as the probe and NIH:OVCAR-3 as the in vivo model, we will develop and evaluate effective radioimmunotherapy for the targeting and elimination of peritoneal ovarian tumor seedings. Adriamycin, a commonly used cytotoxic agent in ovarian cancer, will be conjugated to monoclonal antibody F36/22 for intracavity immunochemotherapy of ovarian tumor. Effectiveness of both therapies will be potentiated by biological response modifiers. The proposed approaches to the use of a unique monoclonal antibody in targeting and therapy of ovarian cancer in a confined cavity compartment with little or no communication with other body compartments will generate defined and useful preclinical information. Additionally, data available most recently have suggested the targeting of a repetitive epitope on a breast cancer mucin by McAb F36/22, which was initially generated against human breast cancer cell lines. Since antibody reagent is already available, an immunoassy can be developed easily and evaluated most efficiently on the association between McAb F36/22 and the breast cancer mucin, and the result will be compared with that obtained from an ovarian cancer mucin previously reported by us. Finally, we will elucidate the antigenic determinant(s) of the human prostate specific antigen (PSA), originally reported from this laboratory and the most effective and FDA approved marker for managment of prostate cancer, in order to increase the efficacy of tumor targeting/therapy by monoclonal antibodies already generated.
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