Immunogenicity is the propensity of a therapeutic protein to induce unwanted immune response toward itself or endogenous proteins. Introduction to Immunogenicity of Therapeutic Proteins Mechanistic insights along with consideration of risk factors involved inspire theoretical strategies to provide antigen-specific, long-lasting effects for maintaining the safety and efficacy of therapeutic proteins. Mitigation strategies for immunogenicity are discussed, including those in general use clinically and those currently in development. A two-wave mechanism of antigen presentation in the immune response toward subcutaneous proteins is described, and interaction with dynamic antigen-presenting cells possessing high antigen processing efficiency and migratory activity may drive immunogenicity. This review attempts to provide an overview of the mechanism of immune response toward proteins administered subcutaneously (subcutaneous proteins) and comments on product-related risk factors related to protein structure and stability, dosage form, and aggregation. Beyond route of administration as a treatment-related factor of immunogenicity, certain product-related risk factors are particularly relevant to subcutaneously administered proteins. Unique immunogenicity challenges of the subcutaneous route have been realized through various preclinical and clinical examples, although subcutaneous delivery has often demonstrated comparable immunogenicity to intravenous administration. Unwanted anti-drug antibody response toward proteins or monoclonal antibodies upon repeated administration is shown to impact the pharmacokinetics and efficacy of multiple biologics. The subcutaneous route of administration has provided convenient and non-inferior delivery of therapeutic proteins compared to intravenous infusion, but there is potential for enhanced immunogenicity toward subcutaneously administered proteins in a subset of patients.
0 Comments
Leave a Reply. |