Ungan, Dennis, Be, Celine, Baczyk, Paulina, Mittermeier, Simon, Lehmann, Sylvie, Wiesmann, Christian, Huber, Thomas, Kolbinger, Frank and Rondeau, Jean-Michel (2025) IL-17A complexes with therapeutic antibodies exhibit distinct size distributions, potentially contributing to clinically observed immunogenicity. mAbs, 17 (1). p. 2575840. ISSN 1942-0870

Abstract

Monoclonal antibodies are established as promising treatment options for a broad range of patients suffering from severe diseases. In some cases, the formation of anti-drug antibodies (ADA) may limit their clinical use and potentially affect safety and efficacy for patients. Despite extensive research, some factors contributing to the immunogenicity of some therapeutic antibodies remain poorly understood. In particular, the immunogenicity potential associated with multivalent antibody formats targeting oligomeric protein antigens has thus far received insufficient attention. Large, target-related immune complexes (TRICs) may be formed that can trigger Fc-mediated downstream effects and have the potential to contribute to the development of an ADA response. Here, we present experimental evidence highlighting the roles of epitope, paratope, and binding geometry in defining the composition and size distribution of TRICs formed by four clinical anti-IL-17 monoclonal antibodies with IL-17A, a homodimeric cytokine. Our findings underscore the importance of conducting in-depth biophysical analyses of TRICs formed by therapeutic antibody candidates targeting multivalent protein antigens, to develop safer and more efficacious treatments.

Item Type:	Article
Keywords:	Cosentyx, immune complexes, IL-17A, ixekizumab, bimekizumab, immunogenicity
Date Deposited:	21 Jan 2026 00:45
Last Modified:	21 Jan 2026 00:45
URI:	https://oak.novartis.com/id/eprint/57818