Abstract 1870: Novel conditionally active bispecific T cell engagers targeting solid tumors

Abstract

Abstract The use of CD3/target bispecific molecules has great therapeutic potential in oncology. This potential, however, is diminished due to severe cytokine release effects as well as serious on-target off-tumor toxicities. Conditionally Active Biologic (CAB) technology is a proprietary platform that generates bispecific antibodies which have no or very little binding to CD3 and to the tumor target antigen (TAA) in healthy tissue (normal physiological conditions), but have strong binding in the context of diseased tissues (tumor microenvironment) based on the glycolytic tumor metabolism (including Warburg effect). Using our CAB technology, we have developed dual-CAB (CAB TAA x CAB CD3) bispecific antibodies targeting two well-established tumor associated antigens, B7H3 and Nectin4. These dual-CAB bispecific antibodies were developed so that they bind to recombinant CD3 and TAA as well as to CD3 and TAA expressing cells under in vitro tumor microenvironment conditions, but not in physiologic conditions. In vitro characterization and in vivo efficacy data of the dual-CAB TAA x CD3 bispecific antibodies targeting B7H3 and Nectin4 will be presented. The CAB technology allows the generation of a new class of potent T-cell engagers with increased safety margin and therapeutic index in the clinic. Citation Format: Haizhen Liu, Jing Wang, Ana Paula G. Cugnetti, Charles Xing, Christina Wheeler, Matthew Lucas, Cathy Chang, Gerhard Frey, William Boyle, Jay Short. Novel conditionally active bispecific T cell engagers targeting solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1870.