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

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

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: heyang@szbl.ac.cn.
  • 5 Drug Discovery, Shanghai Huaota Biopharmaceutical Co. Ltd., Shanghai 201203, China. Electronic address: xiang.zhu@huaota.com.
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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