Abstract 5195: Humanized CD3E,D,G mice: An ideal model for efficacy study of CD3-bispecific antibodies

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Abstract CD3-targeting bispecific antibodies (CD3 bsAb) are designed to simultaneously bind to T cells and tumor cell antigens, leading to T-cell activation, proliferation, and tumor cell death. To create a better animal model for studies of CD3-TCBs, we developed the BALBc-hCD3EDG model by gene editing technology, Briefly, a large human genomic fragment containing CD3E,CD3D,CD3G as well as regulatory elements was introduced into the BALBc mouse genome and animals carrying human CD3E,D,G integration were selected to establish the new strain. The BALBc-hCD3EDG mice have a normal immune system and successfully express human CD3E,CD3D,CD3G on the T cell surface. As expected, cytotoxicity of activity T cells by redirecting with CD3-CD20 bsAb was observed in in vitro T cell-mediated killing assays using an A20 cell expressing human CD20. Furthermore, the growth of subcutaneously engrafted CT26 and hCD20-A20 tumors in BALBc-hCD3EDG mice, was strongly inhibited by CD3-TCB antibody treatment. In conclusion, the CD3EDG humanized mice are ideal models for preclinical studies of bispecific antibodies and other immunotherapies. Citation Format: xiaoliu Yang, cunxiang Ju, mingkun zhang, jing zhao. Humanized CD3E,D,G mice: An ideal model for efficacy study of CD3-bispecific antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5195.