A novel and effective approach to generate germline-like monoclonal antibodies by integration of phage and mammalian cell display platforms

通过整合噬菌体和哺乳动物细胞展示平台来产生种系样单克隆抗体的新颖有效方法

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作者:Yu-Jia Jin, Diao Yu, Xiao-Long Tian, Hui-Xian Li, Xiao-Chao Zhou, Yu Kong, Wei Zhang, Lu Zhang, Cheng Lei, Zhen-Lin Yang, Chao Tu, Yan-Ling Wu, Tian-Lei Ying

Abstract

Phage display technology allows for rapid selection of antibodies from the large repertoire of human antibody fragments displayed on phages. However, antibody fragments should be converted to IgG for biological characterizations and affinity of antibodies obtained from phage display library is frequently not sufficient for efficient use in clinical settings. Here, we describe a new approach that combines phage and mammalian cell display, enabling simultaneous affinity screening of full-length IgG antibodies. Using this strategy, we successfully obtained a novel germline-like anti-TIM-3 monoclonal antibody named m101, which was revealed to be a potent anti-TIM-3 therapeutic monoclonal antibody via in vitro and in vivo experiments, indicating its effectiveness and power. Thus, this platform can help develop new monoclonal antibody therapeutics with high affinity and low immunogenicity.

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