Affinity maturation of antiHER2 monoclonal antibody MIL5 using an epitope-specific synthetic phage library by computational design
Increased affinities mainly equal to improved biological efficacy in many cases.By now, display methods including phage library are widely exploited to obtain higher affinity antibodies.Traditional library methods mainly focus on complementary determining region mutagenesis, in which extensive screening of variant combinations as well as large library capacity is required to find higher affinity clones.In this study, based on the modeling 3D complex structure of antigen (HER2)-antibody (MIL5) complex, the key residues of contact surface were predicted and identified to guide the synthetic phage library design.Then, epitope-specific site-directed mutagenesis phage library comprised of MIL5_scFv mutants was constructed, from which a higher affinity single chain antibody (M5scFv_ph) was screened out.Following experimental results showed that the novel antibody M5scFv_ph retained superimposed epitope to the parent antibody MIL5_scFv, and possessed similar tumor growth inhibitory activity in vivo on ovarian carcinoma xenografts.
affinity maturation epitope-specific phage library HER2/ErbB2 antibody
Chunxia Qiao Ming Lv Xinying Li Jing Geng Yan Li Jiyan Zhang Zhou Lin Jiannan Feng Beifen Shen
Laboratory of Immunology, Institute of Basic Medical Sciences, P.O.Box 130(3), Taiping Road ＃27, Beijing, 100850, China
国内会议
苏州
英文
58-69
2014-10-26（万方平台首次上网日期，不代表论文的发表时间）