Immunogenicity of biotherapeutics-an overview

With the recent increase in the approval and use of biotherapeutics in clinical practice, management of the development of anti-drug antibodies (ADA) has become a key issue for effective long-term use of these drugs. In most instances, the clinical benefit derived from the use of the therapeutics outweighs the risk of developing ADA. In rare instances, however, safety issues accompany development of ADA. Although it is unclear why certain individuals generate an immune response while others tolerate the drug, growing experience from the clinic has facilitated a better appreciation of many patient-, disease- and product-related factors that contribute to immunogenicity. Furthermore, improvements in protein production, purification and delivery methods along with use of humanized or fully human recombinant proteins have helped to reduce the rates of immunogenicity considerably. This document provides an overview of the scientific reasons for developing an immunogenic response, factors that contribute to the immunogenicity of biotherapeutics, clinical impact of immunogenicity and general strategies used to manage this risk.