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Molecular Biology

, Volume 52, Issue 4, pp 543–547 | Cite as

Development and Optimization of Therapeutic Analogues of Anti-TNFα Antibody Infliximab

  • X.-J. Yu
  • Y.-F. Shen
  • J. Dong
  • T. Li
  • C. Wang
  • Y.-J. Zhang
  • L.-F. Wang
  • Y.-C. Meng
  • Y. Yang
  • H.-J. Wang
  • C.-H. Lei
  • S. Hu
  • B.-H. Li
Molecular Cell Biology
  • 21 Downloads

Abstract

Previously, we have reported the crystal structures of Fab fragment of Infliximab in complex with TNFα. The structurally identified epitope on TNFα revealed the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface and the possibility to optimize the binding affinity. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the infliximab epitope. To develop novel anti-TNFα antibodies, structural analysis, the phage display antibody isolation, step by step antibody optimization, CDR residues random mutagenesis, and binding affinity characterization were performed. One of the novel antibodies generated on the backbone of infliximab, Inf3D6, has the superior binding affinity to TNFα, thus, demonstrating the potential for structure guided optimization for improvement of existing antibody-based therapeutics.

Keywords

TNFα infliximab targeted therapy 

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Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • X.-J. Yu
    • 1
    • 2
  • Y.-F. Shen
    • 3
  • J. Dong
    • 4
  • T. Li
    • 3
  • C. Wang
    • 1
  • Y.-J. Zhang
    • 1
  • L.-F. Wang
    • 1
  • Y.-C. Meng
    • 1
  • Y. Yang
    • 1
    • 5
  • H.-J. Wang
    • 1
    • 5
  • C.-H. Lei
    • 3
  • S. Hu
    • 3
  • B.-H. Li
    • 5
  1. 1.International Joint Cancer InstituteSecond Military Medical UniversityShanghaiPeople’s Republic of China
  2. 2.Central LaboratoryNavy General Hospital of PLABeijingChina
  3. 3.Department of Biophysics, College of Basic Medical SciencesSecond Military Medical UniversityShanghaiPeople’s Republic of China
  4. 4.Department of Vascular Surgery, Changhai HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China
  5. 5.Shanghai Key Laboratory for Molecular ImagingShanghai University of Medicine and Health SciencesShanghaiChina

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