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Poster A203: Evaluate Human-Specific TIM-3 Immunotherapeutics In Vivo

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


CrownBio 2017. Poster A203: Evaluate Human-Specific TIM-3 Immunotherapeutics In VivoResearch 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

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