CD40免疫检查点人源化小鼠的制备及在抗体药物研究中的应用

目的 实验动物模型是生物药物开发领域包括肿瘤学研究、抗体药物开发、临床前药效及安全评价等的一种重要工具.制备CD40人源化小鼠能够为CD40抗体的临床前药效、药理研究和安全性评价提供更多的可能.方法 利用CRISPER/Cas9系统制备获得CD40人源化小鼠后,通过RT-PCR以及流式细胞术检测CD40人源化小鼠表达人...

Establishment of CD40 Immune Checkpoint Humanized Mice and Their Application in Antibody Drug Research #br##br#

Abstract: Objective Laboratory animal model is an important tool in the field of biological drug development,including oncology research, antibody drug development and preclinical efficacy and safety evaluation. The aim of this study is to prepare CD40 humanized mice ( B-hCD40 ) and provide more possibilities for preclinicalpharmacodynamics study and safety evaluation of CD40 antibody. Method B-hCD40 mice was constructed byCRISPER / Cas9 system. Then the expression of human CD40 was detected by RT-PCR and flow cytometry. A tumor model was well established basing on B-hCD40. Meanwhile, anti-tumor efficacy and safety of CD40 activatedmonoclonal antibodies were evaluated. Result Human CD40 was only expressed in B-hCD40, and the ratio ofdifferent lymphocytes had no significant differences compared to wild-type mice. CD40 monoclonal antibody could significantly inhibit tumor growth. The weight loss of mice of the treatment group may be caused by the liver andkidney toxicity of the antibody. Conclusion In our study, B-hCD40 were successfully prepared, which is aneffective animal model for evaluating the efficacy and safety of CD40 antibody drugs.