Abstract Vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic factors in modulating tumor microenvironment (TME), and the concentration of VEGF in TME is significantly higher than that of peripheral. Inhibiting VEGF can improve immunotherapy efficacy by modulating the TME, preventing angiogenesis and regulating immune cell populations. Combined anti-VEGF and anti-Programmed cell death protein 1 (PD-1) /Programmed cell death ligand (PD-L1) therapies have exerted potent antitumor effect in preclinic and clinic studies. Therefore, we developed a novel humanized IgG1 silenced bispecific antibody RC148 to target VEGF and PD-1. RC148 allows dimeric VEGF crosslinking and gradually enhances PD-1 binding activity, potentially reduces systemic toxicity of anti-VEGF therapy and enhances antitumor potency via VEGF trigged enrichment in tumor areas. In preclinical studies, RC148 blocks the binding of VEGF to VEGFR and PD-1 to PD-L1, prevents the growth and migration of human umbilical vein endothelial cells, enables efficient T cell activation, exhibited synergistic antitumor effects in rodent models and showed safety profiles in non-human primate studies. Citation Format: Jianmin Fang, Dong Li, Kaiyue Wu, Sisi Wang, Du Li, Guorui Zhao, Shenjun Li, Jing Jiang. RC148, a novel bispecific antibody targeting PD-1 and VEGF for cancer immunotherapy 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 (6Suppl): Abstract nr 2734.
Fang et al. (2024) studied this question.