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

Cellular & Molecular Immunology volume 15, pages 146–157 (2018)Cite this article

Abstract

Currently, display-based methods are well established and widely used in antibody engineering for affinity maturation and structural stability improvement. We obtained a novel anti-human programmed death 1 (PD-1) antibody using computer-aided design and a mammalian cell display technology platform. We 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 PD-1. Then, 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 construction. We 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 residues. The virtual antibody libraries were displayed on the surface of mammalian cells as the antigen-binding fragments of full-length immunoglobulin G. Then, we used flow cytometry and sequencing approaches to sort and screen the candidates. Finally, we obtained a novel anti-human PD-1 antibody named FV78. FV78 competitively recognized the PD-1 epitopes that interacted with MIL75 and possessed an affinity comparable to MIL75. Our 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.

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Acknowledgements

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) and the Beijing Natural Science Foundation (No. 5152022).

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Authors and Affiliations

  1. Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, 100850, China

    Longlong Luo, Xiaoling Lang, Tingting Zhou, Jing Geng, Xinying Li, Chunxia Qiao, Jiannan Feng, Beifen Shen, Ming Lv & Yan Li

  2. Laboratory of Cellular and Molecular Immunology, Institute of Immunology, Henan University, Kaifeng, 475001, China

    Shi Wang

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Correspondence to Ming Lv or Yan Li.

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Luo, L., Wang, S., Lang, X. et al. Selection and characterization of the novel anti-human PD-1 FV78 antibody from a targeted epitope mammalian cell-displayed antibody library. Cell Mol Immunol 15, 146–157 (2018). https://doi.org/10.1038/cmi.2016.38

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