Abstract 230: Improved CD3E Transgenic Mouse Model for I/O Agent Testing

Establishment of a Human CD3ε Transgenic Mouse Model to Assess Antitumor Efficacy of Human T Cell-Redirecting Bispecific Antibodies

Mengmeng Yang, Mingkun Zhang*, Sandra Verploegen#, Patrick Engelberts#, Yuxi Zhang*, Lei Zheng, Keyi Zhu, Annie X. An, Cunxiang Ju*, Jing Zhao*, Xiang Gao*, Henry Q.X. Li, and Davy X. Ouyang

*Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China;
#Genmab B.V., Yalelaan 60, 3584 CM Utrecht, The Netherlands

Preclinical models are required to test T cell-redirecting bispecific antibodies targeting CD3E. However, due to a lack of cross-reactivity between mouse and human CD3E, murine models aren’t appropriate. Knock in mouse models for human CD3E have been previously developed, but the resulting models had defective T cell development rendering them inadequate for pharmacological testing.

CrownBio, in collaboration with NJU, has now developed a new human CD3ε transgenic BAC model in a BALB/c background. The model is phenotypically normal with levels of T, B, and NK cells comparable to those in wild type BALB/c mice, and co-expressing mouse and human CD3E on T cells.

This poster details the development and characterization of the model, with ex vivo T cell stimulation assay data and in vivo efficacy data included.

Read this Poster to Discover:

• That the new CD3E transgenic mouse model offers a novel preclinical platform for assessing the in vivo efficacy of human CD3E T cell-redirecting therapeutics
• That in vivo testing of CD20xCD3 bispecific antibodies demonstrates robust pharmacodynamic effects and efficacies
• How other T cell mediated tumor killing, i.e. mouse PD-L1 antibody (10F.9G2) display similar efficacies in hCD3E transgenic mice as in wild type BALB/c mice bearing H22 murine liver cancer

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