Establishment of a Human CD3ε Transgenic Mouse Model to Assess Antitumour 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 development and evaluation of T cell-redirecting antibodies is often blocked by a lack of appropriate in vivo models. These bispecific antibodies physically link tumour and T cells, usually binding to tumour associated antigens and CD3ε. There’s a lack of cross reactivity between human and mouse CD3ε, therefore standard in vivo immunocompetent murine models cannot be used.
CD3ε humanized models have been previously developed; however, these were not suitable for immunotherapy and antibody assessment due to the blockade of T lymphocyte and natural killer cell development.
This poster details the development of a new preclinical human CD3ε BAC transgenic mouse model which is phenotypically normal, and the validation of this model for T cell-redirecting antibody assessment.
Read this Poster to Discover:
- That CD3ε transgenic mice are phenotypically normal, with levels of T, B, and NK cells comparable to those in wild type mice, therefore suitable for immuno-oncology research and development
- Validation of the model through in vivo testing with CD20xCD3 bispecific antibodies, demonstrating robust in vivo pharmacodynamic effects and efficacies
- That the improved CD3ε transgenic model offers a novel platform for the preclinical in vivo assessment of human CD3ε T cell-redirecting antibodies