title: Epitope mapping reveals the binding mechanism of a functional antibody cross-reactive to both human and murine programmed death 1.
abstract: Of the inhibitory checkpoints in the immune system, programmed death 1 (PD-1) is one of the most promising targets for cancer immunotherapy. The anti-PD-1 antibodies currently approved for clinical use or under development bind to human PD-1 (hPD-1), but not murine PD-1. To facilitate studies in murine models, we developed a functional antibody against both human and murine PD-1, and compared the epitopes of such antibody to a counterpart that only bound to hPD-1. To quickly identify the epitopes of the 2 antibodies, we used alanine scanning and mammalian cell expression cassette. The epitope identification was based on PD-1-binding ELISA and supported by affinity ranking of surface plasmon resonance results. The hPD-1 epitopes of the 2 functional antibodies were also compared with the binding region on hPD-1 that is responsible for PD-L1 interaction. In silico modeling were conducted to explain the different binding modes of the 2 antibodies, suggesting a potential mechanism of the antibody cross-species binding.
authors.affiliation: a Biologics Discovery, WuXi Biologics , Waigaoqiao Free Trade Zone, Shanghai , China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: a Biologics Discovery, WuXi Biologics , Waigaoqiao Free Trade Zone, Shanghai , China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: a Biologics Discovery, WuXi Biologics , Waigaoqiao Free Trade Zone, Shanghai , China.
authors.forename: Zhuozhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: b State Key Laboratory of Lead Compound Research, WuXi AppTec , Waigaoqiao Free Trade Zone, Shanghai , China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gong
authors.affiliation: a Biologics Discovery, WuXi Biologics , Waigaoqiao Free Trade Zone, Shanghai , China.
authors.forename: Jieying
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Biologics Discovery, WuXi Biologics , Waigaoqiao Free Trade Zone, Shanghai , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: b State Key Laboratory of Lead Compound Research, WuXi AppTec , Waigaoqiao Free Trade Zone, Shanghai , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: a Biologics Discovery, WuXi Biologics , Waigaoqiao Free Trade Zone, Shanghai , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping / Q000379:methods*; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D061026:Programmed Cell Death 1 Receptor / Q000737:chemistry*
chemical_list: D000906:Antibodies; C105992:PDCD1 protein, human; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor
keywords: Cross-species binding; Programmed death 1 (PD-1); epitope mapping; functional antibody; modeling