Abstract 1879: A novel dual CAB nectin-4 x CD3 bispecific antibody targeting solid tumors

Abstract

Abstract Nectin-4 is a Ca2+ independent immunoglobulin-like protein that is primarily involved in cell-cell adhesion. Nectin-4 is overexpressed in several tumor types, including breast, lung, urothelial, colorectal, pancreatic, and ovarian cancers. Overexpression of Nectin-4 is associated with multiple aspects of tumor progression such as proliferation, angiogenesis, epithelial to mesenchymal transition, metastasis, DNA repair and tumor relapse. This overexpression is correlated with poor prognosis, making Nectin-4 an attractive target for developing new therapeutic strategies for cancer. As a result, a substantial number of antibody drug conjugates targeting Nectin-4 are under development. Most of these therapies, however, display a high rate of drug related toxicities accentuating the need for alternative approaches for anti-cancer therapeutics targeting Nectin-4. We leveraged BioAtla’s Conditionally Active Biologic (CAB) platform to develop a dual CAB T cell engager (TCE) bispecific antibody targeting Nectin-4 and CD3 receptors (CAB-Nectin-4 x CAB-CD3 bispecific antibody). The dual CAB Nectin-4 x CD3 bispecific antibody was engineered to bind with high affinity to both Nectin-4 and CD3 receptor antigens under conditions that mimic the acidic tumor microenvironment, but with lower binding activity in physiological (alkaline) conditions. In vitro and in vivo efficacy data for a dual-CAB Nectin-4 x CD3 bispecific antibody will be presented. Our data will demonstrate that the dual-CAB bispecific antibody promotes cytotoxicity of Nectin-4-expressing cancer cells in vitro and induces complete tumor regression in vivo. Further, the dual CAB Nectin-4 x CD3 bispecific antibody has higher potency in inducing primary T cell activation measured by means of cytokine release and cancer cell cytotoxicity under acidic conditions compared to the non-CAB benchmark bispecific antibody. Citation Format: Matthew Lucas, Ana Paula Cugnetti, Haizhen Liu, Charles Xing, Jing Wang, Patricia McNeeley, Christina Wheeler, Solmarie Joyner, Kyrie Johnson, Kathryn Woodard, Wei Zhou, Cathy Chang, Gerhard Frey, William J. Boyle, Jay M. Short. A novel dual CAB nectin-4 x CD3 bispecific antibody targeting solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1879.