Abstract 356: Novel conditionally active biologic (CAB) antibody targeting EpCAM demonstrates anti-tumor efficacy in vivo

Abstract

Abstract Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell-cell adhesion during cell signaling, migration, proliferation, and differentiation. EpCAM is expressed at high levels exclusively in epithelia and epithelial-derived neoplasms, making it a suitable target for many important solid tumor types and cancer stem cells. EpCam expression on normal tissues limits its utility as target for therapeutic antibodies and ADCs due to the potential effects on normal epithelial throughout the body. Conditionally Active Biologics (CAB) technology is a proprietary platform that selects antibodies that bind to target antigens in the context of diseased tissues, but not normal tissues, by taking advantage of the unique conditions in the tumor microenvironment. Using our CAB technology, we have developed CAB antibodies to EpCAM that reversibly bind to recombinant EpCAM and EpCAM expressing cells under select conditions that are present in the tumor microenvironment but not in normal tissues. In vitro and in vivo efficacy data for several anti-EpCAM antibodies and ADCs will be presented and suggest that conditionally active EpCam ADCs generated using the CAB technology will provide drug candidates that have an increased safety margin and therapeutic index in the clinic. Citation Format: Cathy Chang, Gerhard Frey, Leslie Sharp, William (Bill) J. Boyle, Jing Wang, Charles Xing, Haizhen Liu, Christina Wheeler, Marlena Walls, Jay M. Short. Novel conditionally active biologic (CAB) antibody targeting EpCAM demonstrates anti-tumor efficacy in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 356.