biostudies-literatureUnknown17(1)Ungan DNovartis Pharma AG, Basel, SwitzerlandMonoclonal antibodies are well established as promising treatment options for a broad range of patients with 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 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 highmAbs2575840https://www.ebi.ac.uk/biostudies/studies/S-EPMC12536631biostudies-literatureIL-17A complexes with therapeutic antibodies exhibit distinct size distributions, potentially contributing to clinically observed immunogenicity.PMC12536631Ungan DBaczyk PWiesmann CMittermeier SKolbinger FRondeau JMBe CHuber TLehmann SfalseIL-17A complexes with therapeutic antibodies exhibit distinct size distributions, potentially contributing to clinically observed immunogenicity.Monoclonal antibodies are well established as promising treatment options for a broad range of patients with 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 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 high2025-01-01T00:00:00Z2025 Dec2026-06-04T14:50:11.182Z2026-05-10T03:11:43.124ZS-EPMC125366314111100410.1080/19420862.2025.2575840