Abstract 2732: NB203: A Novel therapeutic bispecific antibody targeting CEACAM1/VEGF for tumor immunity and angiogenesis modulation in the tumor microenvironment

Abstract The carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is detected on leukocytes, epithelia and endothelia, and involved in cell adhesion through homophilic or heterophilic binding. In various gastrointestinal cancers, NSCLC (non-small cell lung cancer), and melanoma, CEACAM1 is highly expressed on tumor cells and tumor stroma, with its levels increasing as the disease progresses. Notably, CEACAM1 has been found to dampen T and NK cell functions while promoting tumor angiogenesis and metastasis. In this study, we present NB203, a novel CEACAM1/VEGF bispecific antibody developed using Neologics CEACAM-plus, a bifunctional molecule engineering platform designed to target and modulate the tumor microenvironment (TME). NB203 effectively accumulated in the TME and hindered the homophilic or heterophilic interactions of CEACAM1. It demonstrated a significant enhancement in T cell activities and NK cell-mediated killing of CEACAM1-expressing tumor cells, and the inhibition of tumor cell migration and polyploidy through macrophages. More importantly, NB203 was specifically designed to impede tumor angiogenesis. It exhibited an increased binding capacity to both CEACAM1 and VEGF in pro-angiogenic TME, and undermined intratumoral vessel maturation by blocking VEGF and negatively regulating myeloid cell-dependent tumor angiogenesis. In summary, our preclinical data indicate that NB203 exhibits effective anti-tumor activity by mediating NK and cytotoxic T cell activities, improving the immune-suppressive TME, and suppressing tumor angiogenesis. The use of NB203 holds promise in overcoming resistance to anti-VEGF therapy and substantially improving the safety of therapeutic targeting of angiogenesis in cancer treatment. Citation Format: Jinyu Dong, Binbin Wang, Dong Wang, Jie Ni, Tingting Bu, Haojie Wang, Bishnu Nayak, Baiyang Wang, Xin Dong, Yu Zhang. NB203: A Novel therapeutic bispecific antibody targeting CEACAM1/VEGF for tumor immunity and angiogenesis modulation in the tumor microenvironment 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 2732.