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

Yu-jia Jin1, Diao Yu1,2, Xiao-long Tian1, Hui-xian Li2, Xiao-chao Zhou2, Yu Kong1, Wei Zhang1, Lu Zhang2, Cheng Lei2, Zhen-lin Yang3, Chao Tu2, Yan-ling Wu1, Tian-lei Ying1
1 MOE/NHC Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
2 Biomissile Corporation, Shanghai 201203, China
3 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Correspondence to: Yan-ling Wu:, Tian-lei Ying:,
DOI: 10.1038/s41401-021-00707-3
Received: 24 March 2021
Accepted: 25 May 2021
Advance online: 7 July 2021


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.
Keywords: phage display; mammalian cell display; germline-like; monoclonal antibody; TIM-3

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