Abstract 6138: Generation of humanized C1Q mice for antibody-mediated CDC therapy research

Abstract The complement system is an essential part of innate immunity, consisting of more than 30 proteins. A critical element in the pathway is C1q (Complement 1 q), an important recognition molecule in the classical pathway of the complement system that can initiate the classical pathway and plays a major role in bridging innate and adaptive immunity. C1q is also vital in monoclonal antibody (mAb) therapy, as it attaches to the Fc region of antibodies, initiating complement-dependent cytotoxicity (CDC). Here, we generated a humanized C1Q model (B-hC1Q mice), by replacing the murine C1qa, C1qb, and C1qc genes that encode the full-length protein with the corresponding human C1QA, C1QB, and C1QC coding regions. We confirmed the exclusive expression of human C1Q in the serum of the humanized model at levels comparable to those of wild-type murine C1Q. We also performed classical pathway complement activity analysis on B-hC1Q mice, and the results showed that humanized C1Q performed the proper complement function in mice. To evaluate the CDC effector of monoclonal antibodies in eliminating cancer cells, we conducted tumor efficacy experiments using B-hCD38-luc E.G7-OVA cells, engineered to express human CD38, injected via the tail vein into B-hC1Q mice. Treatment with Daratumumab analog effectively abolished tumor growth in humanized C1Q mice. Together, the B-hC1Q mice provide in vivo platforms to evaluate complement system-related disease and CDC effector functions in tumor therapy. Citation Format: James Jin, Ruili Lv, Zan Zhang, Jinyi Ma, Jiangfeng Yuan, Xuan Yu, Zhi Zhang, Jiansu Zhang, Xiaofei Zhou. Generation of humanized C1Q mice for antibody-mediated CDC therapy research [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 6138.