Fichter, Marie, Richter, Gesa, Bepperling, Alexander and Wassmann, Paul (2022) Pre-clinical in-vitro studies on parameters governing immune complex formation. Pharmaceutics.

Abstract

The success of biotherapeutics is often challenged by the undesirable events of immunogenicity in patients, characterized by the formation of anti-drug antibodies (ADA). Under specific conditions, the ADAs recognizing the biotherapeutic can trigger the formation of immune complexes (ICs), followed by cascades of subsequent effects on various cell types. Hereby, the connection between the characteristics of ICs and their downstream impact is still not well understood. Factors governing the formation of ICs and the characteristics of these IC species were assessed systematically in-vitro. Classic analytical methodologies such as SEC-MALS and SV-AUC, and the state-of-the-art technology mass photometry were applied for the characterization. The study demonstrates a clear interplay between 1) the absolute concentration of the involved components, 2) their molar ratios, 3) structural features of the Biologic 4) and of its endogenous target. This surrogate study design is readily applicable to any biotherapeutic and provides valuable insights into mechanisms of IC formation prior to FIH studies. The applicability is versatile – from selection of candidates during developability assessment to evaluation of the impact of degraded or post-translationally modified biotherapeutics on the formation of ICs.

Item Type:	Article
Keywords:	immune complexes; protein complexes; anti-drug antibodies; immunogenicity; biotherapeutics; analytical assessment; aggregation; mass photometry; SEC-MALS; SV-AUC
Date Deposited:	09 Jul 2022 00:45
Last Modified:	09 Jul 2022 00:45
URI:	https://oak.novartis.com/id/eprint/47326