Abstract 1861: Advancing bispecific antibody discovery using common light chain immunoglobulin humanized mouse

Abstract

Abstract The common challenges of bispecific therapeutic antibody discovery are immunogenicity and chain mispairing issues. Biocytogen's RenLiteTM immunoglobulin humanized mouse is designed not only to overcome these two issues, but also to provide a full human heavy chain repertoire diversity. RenLiteTM mouse carries full human heavy chain VDJ loci and a fixed common human light chain VJ gene. The derived antibodies share the same light chain with different heavy chain variable domain. This technology dramatically simplifies the following heavy and light chain pairing process. Antibodies generated by RenLiteTM mice underwent natural selection, differentiation, and affinity maturation in vivo utilizing a human heavy chain repertoire, the potential of immunogenicity is minimized. RenLiteTM mice show robust immune response comparable to wild type mice and RenLiteTM mice derived antibodies have high binding affinity at subnanomolar range. RenLiteTM antibodies also showed strong in vivo efficacy against tumor growth in xenograft mouse models. In summary, RenLiteTM mouse is a powerful tool for advancing current bispecific or multispecific antibody discovery. Citation Format: Li Hui, Hui Lu, Yabo Zhang, Shuwen Huang, Ping Zhang, Huizhen Zhao, Ruifang Chang, Bing Yang, Fengqian Zhang, Wendong Yang, Fang Yang, Hao Yang, Jiawei Yao, Lei Chen, Qingcong Lin. Advancing bispecific antibody discovery using common light chain immunoglobulin humanized mouse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1861.