Nonclinical immunogenicity risk assessment of therapeutic proteins.

Therapeutic protein drugs have significantly improved the management of many severe and chronic diseases. However, their development and optimal clinical application are complicated by the induction of unwanted immune responses. Therapeutic protein-induced antidrug antibodies can alter drug pharmacokinetics and pharmacodynamics leading to impaired efficacy and occasionally serious safety issues. There has been a growing interest over the past decade in developing methods to assess the risk of unwanted immunogenicity during preclinical drug development, with the aim to mitigate the risk during the molecular design phase, clinical development and when products reach the market. Here, we discuss approaches to therapeutic protein immunogenicity risk assessment, with attention to assays and in vivo models used to mitigate this risk.