IL-17A functions and the therapeutic use of IL-17A and IL-17RA targeted antibodies for cancer treatment

Int Immunopharmacol. 2023 Oct:123:110757. doi: 10.1016/j.intimp.2023.110757. Epub 2023 Aug 12.

Abstract

Interleukin 17A (IL-17A) is a major member of the IL-17 cytokine family and is produced mainly by T helper 17 (Th17) cells. Other cells such as CD8+ T cells, γδ T cells, natural killer T cells and innate lymphoid-like cells can also produce IL-17A. In healthy individuals, IL-17A has a host-protective capacity, but excessive elevation of IL-17A is associated with the development of autoimmune diseases and cancer. Monoclonal antibodies (mAbs) targeting IL-17A (e.g., ixekizumab and secukinumab) or IL-17A receptor (IL-17RA) (e.g., brodalumab) would be investigated as potential treatments for these diseases. Currently, the application of IL-17A-targeted drugs in autoimmune diseases will provide new ideas for the treatment of tumors, and its combined application with immune checkpoint inhibitors has become a research hotspot. This article reviews the mechanism of action of IL-17A and the application of anti-IL-17A antibodies, focusing on the research progress on the mechanism of action and therapeutic blockade of IL-17A in various tumors such as colorectal cancer (CRC), lung cancer, gastric cancer and breast cancer. Moreover, we also include the results of therapeutic blockade in the field of cancer as well as recent advances in the regulation of IL-17A signaling.

Keywords: Brodalumab; Cancer; Interleukin-17A; Ixekizumab; Secukinumab.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases*
  • CD8-Positive T-Lymphocytes
  • Humans
  • Immunity, Innate
  • Interleukin-17
  • Neoplasms* / drug therapy
  • Th17 Cells

Substances

  • Interleukin-17
  • IL17A protein, human