Abstract 1891: Identifying new therapeutic antibodies using the RenMice™ HiTS Platform

Abstract Over the past decade, an increasing number of therapeutic antibodies have been approved to target cancer. However, the process of identifying new therapeutic antibodies is routinely hampered by limitations in the traditional discovery process, including immune tolerance of highly homologous genes, and challenges with antibody sequence humanization, clone selection and drug efficacy and safety evaluation. RenMice™ HiTS (Hyperimmune Target Specific) is a collection of chromosome engineered mice with fully human immunoglobulin variable domains replacing mouse counterparts, each with a specific drug target gene knocked out. The goal of the RenMice™ HiTS platform is to overcome the challenges of traditional antibody drug discovery and increase the diversity of antibody paratopes and sequences which recognize functional epitopes. Immunization of target-specific RenMice™ generates a greater diversity of antibodies, including those that recognize the conserved regions between the antigen and the endogenous proteins of the immunized host. The platform is ideal for challenging targets, such as proteins with high homology between human and mouse, or multi-pass transmembrane proteins (eg. GPCRs/ion channels). The platform can be used to generate antibodies that cross-react with human, monkey, dog, and mouse targets, using a hybrid immunization strategy with both human and mouse/dog antigen. Generation of these species cross-reactive antibodies allows for high-throughput in vivo efficacy screening using wild-type mice. It is also possible to predict the preliminary response and toxicity in dogs with these cross-reactive antibodies. Thus, selection of the best antibody candidate based on in vivo efficacy and safety allows for a streamlined and successful preclinical phase. In conclusion, the RenMice™ HiTS platform facilitates the generation of antibodies with better developability properties that recognize challenging targets and novel epitopes. Citation Format: Xiaoqian Zhang, Shujin Zhang, Tianquan Jin, Xin Ji, Jing Zhang. Identifying new therapeutic antibodies using the RenMice™ HiTS Platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1891.