The establishment and application of CD3E humanized mice in immunotherapy

In the field of cancer immunotherapy, monoclonal antibody drugs, bispecific antibodies, and antibody-conjugated drugs have become the focus of current research, and gene-edited animal models play an essential role in the entire drug development process. In this study, CD3E humanized mice were establ...

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Bibliographic Details
Published in:Experimental Animals 2022, Vol.71(4), pp.442-450
Main Authors: Zhang, Rufeng, Zhang, Jing, Zhou, Xiaofei, Zhao, Ang, Yu, Changyuan
Format: Article
Language:English
Subjects:
Animal models
Bispecific antibodies
Cancer immunotherapy
CD3E
Cell activation
Cell death
Drug development
Drugs
Flow cytometry
Gene expression
Genetic modification
humanized mouse model
Immunotherapy
Lymphocytes
Monoclonal antibodies
monoclonal antibody
Pharmacodynamics
Tumors
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Summary:In the field of cancer immunotherapy, monoclonal antibody drugs, bispecific antibodies, and antibody-conjugated drugs have become the focus of current research, and gene-edited animal models play an essential role in the entire drug development process. In this study, CD3E humanized mice were established by replacing the second to the seventh exon of the Cd3e mouse gene with the same exon of the human gene. The expression of human CD3E in CD3E humanized mice was detected by RT-PCR as well as flow cytometry, also a tumor model was established based on CD3E humanized mice, and the pharmacodynamic effects of CD3E monoclonal antibodies were evaluated. The results showed that CD3E humanized mice expressed only human CD3E, and the proportion of each lymphocyte in the thymus and spleen was not significantly changed compared with wild-type mice. CD3E monoclonal antibody could promote tumor growth after treatment, which may be related to the activation-induced cell death effect caused by this CD3E antibody. In contrast, Bispecific antibody blinatumomab inhibited tumor growth significantly. Thus, the CD3E humanized mice provided an adequate animal model for evaluating the efficacy and safety of CD3E antibody drugs.
ISSN:1341-1357
1881-7122
DOI:10.1538/expanim.22-0012