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. Epub 2022 Jan 20.

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Autoimmune Diseases* / drug therapy
  • Humans
  • Interleukin-17
  • Macaca fascicularis / metabolism
  • Mice
  • Psoriasis* / drug therapy

Substances

  • Antibodies, Monoclonal
  • Interleukin-17