LAUSR

There is a need for the development of better targeted therapies in the treatment of ovarian cancer. Monoclonal antibodies directed towards MUC16, a diagnostic and prognostic marker for ovarian cancer, with improved selectivity and specificity would be an instrumental component in the construction of novel methods of drug delivery and immunotherapies. C57BL/6 mice were immunized with various MUC16 peptides and truncated MUC16 constructs to extend the scope of MUC16 epitopes within the proximal COOH portion of the retained elements. Three rounds of hybridomas were made from harvested murine splenocytes, and subsequent rounds of peptide-based ELISA and cell-based flow cytometry were performed to select the most promising subclones from each of the fusions. Over 50 hybridomas producing antibodies against MUC16 have been identified and screened for reactivity with MUC16 peptide sequences and native, full-length MUC16 protein presented on the surface of ovarian cancer cell line cells. The antibodies were isotyped, and 10 have been selected for initial characterization. Non-overlapping epitopes were mapped via sequential and tandem peptide-based ELISA. With improved selectivity and specificity, these monoclonal antibodies will be used in the construction of antibody drug conjugates (ADCs) as potential targeted therapies in the treatment of ovarian cancer. Efficacy testing of the candidate antibodies in Matrigel invasion and direct growth inhibition assays is underway. Comparative effectiveness of the binding, internalization, and killing by ADCs in ovarian cancer cell lines will be presented. Antibodies against key MUC16 epitopes may have value in the development of antigen directed therapy. Citation Format: Ian Laster, Oladapo Yeku, David Spriggs. Development of novel and improved monoclonal antiMUC16 antibodies for the targeted therapy of ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3374.