Abstract 2379: The bispecific antibody KA-3007 against B7H3 and CD28 enhances T cell activation in solid tumors

Abstract

Abstract Immunotherapy, revolutionizing the treatment of advanced solid tumors by blocking PD1 signaling, faces challenges as most cancers remain unresponsive to anti-PD-1 therapy. CD28, a key immune co-stimulatory receptor on T cells, often lacks ligands expressed on tumor cells. B7H3 is highly expressed in various solid tumors. In this study, we developed a bispecific antibody (BsAb) named KA-3007, targeting B7H3 and human CD28 to activate T cells in the tumor microenvironment. KA-3007, featuring an identical light chain, was developed using our common light chain bispecific antibody discovery platform with knob-into-hole technology. This BsAb is in regular IgG1 format with mutations in the Fc domain to eliminate ADCC, ADCP, and CDC activity. Its two Fabs bind to B7H3 with high affinity and CD28 with relatively low affinity. Co-culturing T cells with tumor cells expressing B7H3 enhances T cell activation. In PBMC humanized immunodeficient mouse tumor models, KA-3007 effectively suppresses the growth of NCI-H292 tumors, with or without a PD1 antagonist antibody. Furthermore, this antibody exhibits a half-life of more than five days in the blood of Balb/c mice. Finally, we assessed the developability of KA-3007 with different treatments such as high concentration, low pH, repeated freezing and thawing, and high temperature, and it shows neither aggregation nor degradation. In conclusion, the BsAb KA-3007, developed with our common light chain antibody discovery platform, emerges as a promising pre-clinical candidate drug for the treatment of solid cancers. Citation Format: Guojin Wu, Zhengcheng Guo, Hao Peng, Feng Hao, Feng He, Jinying Ning. The bispecific antibody KA-3007 against B7H3 and CD28 enhances T cell activation in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2379.