Therapeutic Targeting of IL-17 and IL-23 Cytokines in Immune-Mediated Diseases

Abstract

The discovery of the biological functions of the interleukin-23/-17 axis led to the identification of IL-23 and IL-17 as important participants in the pathogenesis of several immune-mediated diseases. Therapeutic agents targeting these cytokines and/or their receptors have now been developed as potential treatment strategies for common immune-mediated diseases. Anti-IL-17 and anti-IL-12/-23 regimens appear particularly effective in psoriasis, with promising results in spondyloarthropathies also emerging. Overall, these agents appear well tolerated, with adverse-event rates that are commensurate with those in other biologic treatment programs. The strategic utility of these new agents, however, remains uncertain, and further studies will be required to determine their place in the context of existing conventional and biologic immune-modifying agents.

Th17 immune microenvironment in Epstein-Barr virus–negative Hodgkin lymphoma: implications for immunotherapy

“…Th17-mediated inflammation can be productive in eliminating pathogens, or can be pathogenic in autoimmunity and carcinogenesis. [38][39][40] In the current study, EBV 2 CHL specimens overexpressed the IL-23 receptor, a required component for IL-23-driven STAT3 activation in T cells and a hallmark of the pathogenic Th17 phenotype. 27,41 They also overexpressed genes encoding the proinflammatory cytokines IL-17A (the canonical Th17 cytokine) and IL-1a.…”

“…mAbs blocking IL-17A (secukinumab, ixekizumab) or IL-23 (ustekinumab) are currently in clinical use for patients with moderate to severe psoriasis, and additional drugs blocking the IL-23/IL-17 pathway are in testing for a variety of autoimmune disorders, including rheumatoid arthritis and Crohn disease. 27,39 Of note, none of the 32 CHL patients whose tumors were characterized in the current study received anti-PD-1 therapy. Therefore, the preliminary results presented here warrant further investigation to address potential correlations of tumor response or resistance with EBV status, and with expression of a pathogenic Th17 profile, in CHL patients receiving anti-PD-1 monotherapy.…”

Drug development in the era of precision medicine

“…These pleiotropic genes were of particular interest given their potential as targets for blockbuster drugs treating several diseases 19 . Monoclonal antibodies targeting interleukin-23 (IL-23) and/or IL-12 (along with the downstream cytokine IL-17) for the treatment of various immune-mediated conditions are already used clinically or are in clinical trials with promising results 26–31 (NCT02407223, NCT02204397 and NCT02698475).…”

Vaccine development for rheumatoid arthritis

“…IL-23 is a pro-inflammatory cytokine required for the development of T h 17 cells [41]. IL-23 shares a subunit with IL-12 known as IL-12/23p40 and comprises a specific subunit of IL-23p19.…”