A mechanistic marker-based screening tool to predict clinical immunogenicity of biologics.

ABSTRACT: The efficacy and safety of therapeutic proteins are undermined by immunogenicity driven by anti-drug antibodies. Immunogenicity risk assessment is critically necessary during drug development, but current methods lack predictive power and mechanistic insight into antigen uptake and processing leading to immune response. A key mechanistic step in T-cell-dependent immune responses is the migration of mature dendritic cells to T-cell areas of lymphoid compartments, and this phenomenon is most pronounced in the immune response toward subcutaneously delivered proteins. The migratory potential of monocyte-derived dendritic cells is proposed to be a mechanistic marker for immunogenicity screening. Following exposure to therapeutic protein in vitro, dendritic cells are analyzed for changes in acti

SUBMITTER: Jarvi NL 

PROVIDER: S-EPMC10709359 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature