ENA20 Poster 29: New Human GITR Knock-In Model for Preclinical Efficacy Studies

GITR Agonist Sensitizes MC38/OVA Tumors to CTLA-4 Treatment by Attenuating Tregs in GITR HuGEMM™

Daniel X. He, Chenpan Nie, Lei Zheng, Annie X. An, Henry Q.X. Li, Davy X. Ouyang

GITR plays a vital role in T cell proliferation and antitumor activity, and GITR agonistic antibodies are now being clinically tested in combination with immune checkpoint inhibitors.

There are, however, a lack of preclinical models available for evaluating the efficacy of therapeutic GITR agonistic antibodies, which don’t usually cross bind to mouse targets. To meet this need, we’ve developed a human GITR knock-in model, with the mouse GITR extracellular domain replaced with its human counterpart.

This poster presentation details model characterization, efficacy data for single agent and combination anti-mCTLA-4 and anti-hGITR treatment, immunoprofiling data, and rechallenge studies.

Download this Poster to Discover:

• How a human GITR knock-in model provides a powerful preclinical tool to evaluate the efficacy of human GITR antibodies or their combination with anti-CTLA-4 agents or other immune modulators
  
  
• That humanized GITR expression on splenocyte-derived T cells of GITR knock-in mice recapitulates endogenous mGITR expression on wild-type mice and hGITR expression in human PBMC
  
  
• How treatment of MC38-OVA syngeneic tumors with combination anti-CTLA-4 and anti-hGITR antibodies led to >100% tumor growth inhibition, and subsequent rechallenge studies

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