Generation of Human TIM-3 Knock-In Mice for Preclinical Efficacy Assessment of Therapeutic Antibodies
Lei Zheng, Xuesong Huang, Wenyi Ouyang, Gang Chen*, Annie Xiaoyu An, Jean-Pierre Wery, Jay Liu*, Xin Dong*, Qian Shi, and Davy Xuesong Ouyang
*Nanjing Galaxy Biopharmaceutical Co. Ltd., Nanjing, China
Research is currently ongoing on how to improve the low overall response rate to checkpoint inhibitors, potentially through combination with other immunotherapeutics or new checkpoint targets e.g. TIM-3. TIM-3 and PD-1 co-expression is often associated with an exhausted phenotype of tumor infiltrating lymphocytes, and TIM-3 expression has been reported as a compensatory mechanism in PD-1 non-responsive patients.
Simultaneously targeting PD-1 and TIM-3 is currently being evaluated in clinical trials; however, we are lacking animal models that can efficiently evaluate the efficacy of therapeutic TIM-3 antibodies and combination regimens.
CrownBio has therefore developed a human TIM-3 knock-in mouse model, with exons 2-5 of the mouse HAVCR2 gene replaced with the human counterpart. The mouse model expresses chimeric TIM-3 on stimulated CD4 and CD8 T cells, which is recognized by human TIM-3 antibodies, allowing specific in vivo evaluation.
Read this Poster to Discover:
- That efficacy testing of human TIM-3 antibodies leads to modest tumor growth inhibition of MC38 tumors, which is improved via combination anti-TIM-3 and PD-1 treatment
- That combination of the TIM-3 model with a human PD-L1 expressing MC38 syngeneic cell line allows anti-TIM-3 and PD-L1 combination assessment
- The wide variety of other humanized target models currently under development for human-origin immunotherapeutic assessment