Structural and functional insights into a novel pre-clinical-stage antibody targeting IL-17A for treatment of autoimmune diseases

  • Int J Biol Macromol. 2022 Mar 31:202:529-538. doi: 10.1016/j.ijbiomac.2022.01.119.
Jin-Gen Xu  1 ,  Huifeng Jia  1 ,  Shi Chen  1 ,  Jingyue Xu  1 ,  Yifan Zhan  1 ,  Haijia Yu  1 ,  Wei Wang  2 ,  Xi Kang  3 ,  Xiaopei Cui  1 ,  Yujie Feng  1 ,  Xiaofang Chen  1 ,  Wei Xu  1 ,  Xianfei Pan  1 ,  Xiaoyue Wei  1 ,  Hui Li  1 ,  Yanting Wang  1 ,  Simin Xia  1 ,  Xiaoyan Liu  1 ,  Lixiang Yang  2 ,  Yang He  4 ,  Xiangyang Zhu  5
Affiliations
  • 1. Drug Discovery, Shanghai Huaota Biopharmaceutical Co. Ltd., Shanghai 201203, China.
  • 2. BayRay Innovation Center, Shenzhen Bay Laboratory, Shenzhen 518055, China.
  • 3. Institute of Translational Research, Shenzhen Bay Laboratory, Shenzhen 518055, China.
  • 4. BayRay Innovation Center, Shenzhen Bay Laboratory, Shenzhen 518055, China. Electronic address: [email protected].
  • 5. Drug Discovery, Shanghai Huaota Biopharmaceutical Co. Ltd., Shanghai 201203, China. Electronic address: [email protected].
PMID: 35066019 DOI: 10.1016/j.ijbiomac.2022.01.119
Abstract

The pro-inflammatory cytokine interleukin-17A (IL-17A) is a key driver of multiple inflammatory and immune disorders. Therapeutic antibodies targeting IL-17A have been proven effective in treating patients with these diseases; however, large variations in clinical outcomes have been observed with different antibodies. In this study, we developed HB0017, a novel monoclonal antibody that targets human IL-17A. HB0017 specifically and strongly bound to human, cynomolgus monkey, and mouse IL-17A at the physiological interface with the IL-17A receptor. In human and monkey cells, HB0017 potently antagonized the functions of IL-17A through competitive binding. HB0017 functioned equivalently to that of clinically approved antibodies in terms of therapeutic efficacy for inflammatory disorders and psoriasis in a mouse model. The results indicate that HB0017 may be an alternative biological therapy for treating patients with inflammation and autoimmune diseases.

Keywords
Anti-inflammatory; Crystal structure; HB0017; IL-17A monoclonal antibody; Psoriasis.
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