Characterization of novel anti-IL-26 neutralizing monoclonal antibodies for the treatment of inflammatory diseases including psoriasis. Issue 8 (17th November 2019)

• Record Type: Journal Article
• Authors: Hatano, Ryo; Ito, Takumi; Otsuka, Haruna; Okamoto, Sayo; Komiya, Eriko; Iwata, Satoshi; Aune, Thomas M.; Dang, Nam H.; Kuwahara-Arai, Kyoko; Ohnuma, Kei; Morimoto, Chikao
• Is Part Of: MAbs. Volume 11:Issue 8(2019)
• Page Start: 1428
• Page End: 1442
• Publication Date: 2019-11-17
• Subjects: Interleukin-26 -- monoclonal antibody -- neutralization -- chronic inflammatory diseases -- psoriasis; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2019.1654305
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: Interleukin (IL)-26, known as a Th17 cytokine, acts on various cell types and has multiple biological functions. Although its precise role still remains to be elucidated, IL-26 is suggested to be associated with the pathology of diverse chronic inflammatory diseases such as psoriasis, inflammatory bowel diseases and rheumatoid arthritis. To develop novel neutralizing anti-human IL-26 monoclonal antibodies (mAbs) for therapeutic use in the clinical setting, we immunized mice with human IL-26 protein. Hybridomas producing anti-IL-26 mAbs were screened for various in vitro functional assays, STAT3 phosphorylation and antibiotic assays. Although the IL-20RA/IL-10RB heterodimer is generally believed to be the IL-26 receptor, our data strongly suggest that both IL-20RA-dependent and -independent pathways are involved in IL-26-mediated stimulation. We also investigated the potential therapeutic effect of anti-IL-26 mAbs in the imiquimod-induced psoriasis-like murine model using human IL-26 transgenic mice. These screening methods enabled us to develop novel neutralizing anti-human IL-26 mAbs. Importantly, administration of IL-26-neutralizing mAb did not have an effect on the antimicrobial activity of IL-26. Taken together, our data strongly suggest that our newly developed anti-human IL-26 mAb is a potential therapeutic agent for the treatment of diverse chronic inflammatory diseases including psoriasis.