NEW DIAGNOSTIC/MONITORING ASSAYS FOR OVARIAN CANCER

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COGS Diagnostics plans to develop three new test kits to determine their usefulness for monitoring and/or diagnosis of ovarian cancer patients. Three novel serine proteases overexpressed in ovarian carcinoma have been cloned and sequenced and patents have been filed for composition, diagnostic and therapeutic use. The proteases have been shown; 1) to be overexpressed in early stage disease, 2) to represent all subtypes of ovarian carcinoma including mucinous tumors; 3) to possess either secretion signal sequences or transmembrane domains such that the proteins are placed in the extracellular space; 4) by immunohistochemical localization found to be present in tumor cells and 5) transcripts of all 3 genes were also present in abundance in ovarian carcinoma extracts, but not in normal ovary and either not at all or at very low levels in normal adult tissues. We plan therefore, to develop new ELISA assays representing each protease to determine the value of these tests relative to CAl25 for the detection and monitoring of ovarian carcinoma. It is proposed to produce recombinant proteases in either E. coli or yeast to provide antigen for both monoclonal and polyclonal antibody production. From these reagents, ELISA assays will be configured and evaluated by testing antigen levels in the sera of normal women, women with benign disease and women with ovarian carcinoma. Assays which prove more efficacious than the CA125 assay for either better monitoring of all ovarian tumors, earlier detection of ovarian carcinoma or more specific relationship between tumor presence and serum antigen levels will be further developed for beta site testing and FDA approval. PROPOSED COMMERCIAL APPLICATIONS: There presently exists an estimated $100,000,000 market for CA125 to monitor tumor burden and tumor recurrence. CA125 has provided limited capacity for early diagnosis (equals approximately 50% of stages I & II) and is poorly expressed in mucinous ovarian tumors (10-15% of ovarian cancers). New tests which surpass the limitations of CA125 offer the opportunity to enter an even larger market for monitoring and early diagnosis of ovarian cancer. Assays for novel serine proteases described here offer other applications in research and clinical care e.g. assaying the role of proteases in tumor growth and progression, and evaluating prognostic factors which may identify patients for vaccines or inhibition drug therapy.