SITC 2023 Poster 447

Evaluation of Efficacy and Toxicity of Human CD40 Agonists in C57BL/6-hCD40/hFcγRIIB HuGEMM^™

Demi X. Liu, Kaixia Lian, Xuefei Yan, Lily Rong Wang, Jie Lin, Xinhe Feng, Xiaolong Tu, Chengcheng Wang, Lei Zheng, Xiaoxi Xu, Annie Xiaoyu An, Ludovic Bourre, Jessie JingJing Wang

Crown Bioscience, 16550 West Bernardo Drive, Building 5, Suite 525, San Diego, CA 92127, USA

This research describes a study aimed at evaluating both the efficacy and the irAE of an anti-CD40 human agonist in preclinical studies.

For the purpose of this study, we established a HuGEMM^™ mouse model in which both human CD40 and FcγRIIB were knock-in expressed on C57BL/6 background (C57BL/6-hCD40/hFcγRIIB).

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• A successfully generated humanized C57BL/6-hCD40/hFcγRIIB dKI mouse model (HuGEMM^™) and normal expression of human CD40 and FcγRIIB in these mice.
  
  
• Human CD40 and FcγRIIB receptors are functional upon agonist anti-hCD40 antibody stimulation both in vitro and in vivo.
  
  
• This mouse model was successfully used for the evaluation of human FcγRIIB enhanced hCD40-targeted antibody efficacy and irAE.

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