ABSTRACT
This chapter describes product- and patient-specific factors that can affect the immunogenicity of therapeutic protein products. It outlines and recommends adoption of a risk-based approach to evaluating and mitigating immune responses to or adverse immunologically related responses associated with therapeutic protein products that affect their safety and efficacy. During therapeutic protein product development, elucidation of a specific underlying immunologic mechanism for immunologically related adverse events is encouraged, because this information can facilitate the development of strategies to help mitigate their risk. Neutralizing antibodies can block the efficacy of therapeutic protein products by specifically targeting domains critical for efficacy. Foreign proteins intended for therapeutic use should be evaluated for molecular regions that bear strong homology to endogenous human proteins. Immune responses directed to the intact protein product, but not reactive with either of the separate partner proteins, may be targeting novel epitopes in the fusion region.
