Abstract 4786: A humanized monoclonal antibody targeting the Ig-like V1-C1 domains of B7-H3 suppresses the growth of breast cancer

Abstract Breast cancer, characterized by its heterogeneity and complexity, poses a significant threat to life. Current monoclonal antibody drugs for breast cancer primarily target HER2, which is only present in 15%-25% of all breast cancer cases. Recently, immune checkpoint therapy has emerged as a groundbreaking approach to reactivating anti-tumor immune responses. B7-H3 (CD276), a newly identified member of the B7 family, is expressed in various tumor tissues, making it an attractive candidate for therapeutic intervention. Utilizing advanced antibody discovery platforms, we have developed a humanized monoclonal antibody targeting B7-H3. This antibody exhibits specific binding affinity to epitopes in the Ig-like V1-C1 domain and demonstrates significant antibody-dependent cellular cytotoxicity effects on triple-negative breast cancer and trastuzumab-resistant HER2+ breast cells. Furthermore, both HER2+ cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models indicated that this antibody displayed potent in vivo anti-tumor activity. RNA-seq analysis of mouse tumor tissues revealed that the B7-H3 antibody downregulates the MAPK and NF-κB signaling pathways, leading to reduced tumor cell metabolism and migration, as well as diminished inflammation and cytokine release. Our findings indicate that B7-H3 is a viable therapeutic target, supporting the continued development of related therapeutic agents in both preclinical and clinical settings. This work is supported by FDCT/009/2023/RIC. Citation Format: Fengjuan Zhang, Qi Zhao. A humanized monoclonal antibody targeting the Ig-like V1-C1 domains of B7-H3 suppresses the growth of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4786.