AACR 2023 Poster 4168

BALB/c-CD3EDG HuGEMM™ Mouse Model for Evaluation of CD3-Targeted Tumor Immunotherapy

Demi X. Liu, Kaixia Lian, Xuefei Yan, Jun Zhou, Jie Lin, Lei Zheng, Xiaoxi Xu, Annie Xiaoyu An, Ludovic Bourre, Jessie JingJing Wang
Crown Bioscience Inc., 16550 West Bernardo Drive, San Diego, CA 92127

T cell immune response plays critical roles in cancer immunotherapy. The CD3 complex, composed of CD3ε, CD3δ and CD3γ chains, is an essential component of TCR-CD3 complex mediating TCR signaling. Clinically relevant animal models for proper evaluation of human CD3 antibodies are in great demand in the field. Currently, adoptive transfer of human CD3+ T cells or transplantation of human hematopoietic stem/precursor cells to immunodeficient mice are usually employed. However, these mouse models are not fully immunocompetent and have some limitations. This study evaluated the in vitro CD3EDG functionality and in vivo therapeutic efficacy in BALB/c-hCD3EDG knock-in mouse in which all the three components of the mouse CD3 complex are replaced by their human counterparts, hCD3E, hCD3D and hCD3G.

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• Methods for generating a humanized CD3EDG mouse model (HuGEMM)
  
  
• Expression data, growth characterization, and TCR functionality of CD3EDG HuGEMM
  
  
• Treatment response to hCD3-targeted bispecific antibody

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