PSMA is a prostate-specific membrane bound protein antigen which is defined by the murine monoclonal antibody 7E11.C5. PSMA is highly expressed in prostatic carcinomas, particularly in the more resistant and aggressive clones of cells which appear as the disease progresses. The 7E11.C5 antibody has been successfully applied to immunoscintigraphy to aid in the localizing of metastatic disease. Because of the high tissue specificity of this antigen and the existence of appropriate monoclonal antibodies, the proposed experiments are intended to test the potential of immunotoxin therapy as a means for controlling the disease. Experiments will utilize both tissue culture systems and animal models to assess the potential of this modality to be expanded upon in future research. These experiments will test cell killing by immunotoxin in expressing and non-expressing human prostate cell lines. Based on these results, immunotoxin challenge of INCaP cells inoculated into nude mice will be tested, along with an analysis of the effect of immunotoxin administration on growing INCaP tumors in nude mice. The results of these experiments will provide definitive evidence relating to the future value of immunotoxin use based on the PSMA antigen for prostate cancer treatment in a clinical setting. PROPOSED COMMERCIAL APPLICATION: Immunotoxin therapy represents a potentially effective modality for treatment of prostatic carcinoma. This approach based upon the PSMA antigen and appropriate antibodies is very attractive given the tissue specificity of the antigen and its increase in aggressive cell clones as progression occurs. Significant commercial potential exists in clinical applications based upon this technology.
Thesaurus Terms:cell growth regulation, immunotoxicity, membrane protein, neoplastic growth, prostate neoplasm, prostate specific antigen cytotoxicity, genetic marker, monoclonal antibody, neoplasm /cancer immunotherapy, nonhuman therapy evaluation, protein purification athymic mouse, high performance liquid chromatography, male, ricin, tissue /cell cultureNational Cancer Institute (NCI)
