Selection and characterization of the novel anti-human PD-1 FV78 antibody from a targeted epitope mammalian cell-displayed antibody library

作     者：Longlong Luo Shi Wang Xiaoling Lang Tingting Zhou Jing Geng Xinying Li Chunxia Qiao Jiannan Feng Beifen Shen Ming Lv Yan Li 

作者机构：Laboratory of ImmunologyInstitute of Basic Medical SciencesBeijing100850China Laboratory of Cellular and Molecular ImmunologyInstitute of ImmunologyHenan UniversityKaifeng475001China 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2018年第15卷第2期

页      面：146-157页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：The work was supported by the National Natural Sciences Foundation of China grant(No.81272528 and No.31370938) National High Technology Research and Development Program(863 Program,No.2012AA02A302) National Science and Technology Major Projects for'Major New Drugs Innovation and Development'(2014ZX09304311-001-002-004) the Beijing Natural Science Foundation(No.5152022) 

主　　题：antibody computer-guided modeling distance geometry human PD-1 mammalian cell-displayed antibody library 

摘      要：Currently,display-based methods are well established and widely used in antibody engineering for affinity maturation and structural stability *** obtained a novel anti-human programmed death 1(PD-1)antibody using computer-aided design and a mammalian cell display technology *** used computer-aided modeling and distance geometry methods to predict and assign the key residues that contributed to the binding of human PD-L1 to ***,we analyzed the sequence of nivolumab(an anti-human PD-1 antibody,referred to as MIL75 in the article)to determine the template for antibody design and library *** identified a series of potential substitutions on the obtained template and constructed a virtual epitope-targeted antibody library based on the physicochemical properties and each possible location of the assigned key *** virtual antibody libraries were displayed on the surface of mammalian cells as the antigen-binding fragments of full-length immunoglobulin ***,we used flow cytometry and sequencing approaches to sort and screen the ***,we obtained a novel anti-human PD-1 antibody named ***78 competitively recognized the PD-1 epitopes that interacted with MIL75 and possessed an affinity comparable to *** results implied that FV78 possessed equivalent bioactivity in vitro and in vivo compared with MIL75,which highlighted the probability and prospect of FV78 becoming a new potential antibody therapy.