Poster 5669: CD3E Transgenic Mouse Model for Bispecific Antibody 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

T cell-redirecting therapy is taking a prominent role in immuno-oncology. Recent research has involved the development of T cell-redirecting bispecific antibodies, which bind to a specific tumor associated antigen (TAA) on tumor cells and CD3 (usually epsilon chain, CD3ε) on T cells. This physically links the tumor cell to the T cell which leads to MHC-independent recognition and killing of cells expressing the TAA.

However, research on new therapeutic T cell-redirecting antibodies is often hampered by a lack of appropriate in vivo models, due to the absence of cross-reactivity with mouse CD3ε. To meet this need, we have developed a human CD3ε BAC transgenic model in a BALB/c background.

The transgenic mice express both human and mouse CD3ε on more than 80% of T cells, and, unlike previously developed transgenic lines, the model is phenotypically normal with levels of T, B, and NK cells comparable to those in wild type BALB/c mice.

Read this Poster to Discover:

• That T cells from the transgenic mice can be activated by both human and mouse anti-CD3ε antibodies
• How in vivo testing of CD20xCD3 bispecific antibodies demonstrates robust PD effects and efficacy
• That this transgenic model offers a novel platform to assess the preclinical in vivo efficacy of human CD3E T cell-redirecting therapeutics

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