Unwanted immunogenicity, i.e., the developpement by patients of anti-drug antibodies is a significant problem with biologicals therapeutic reagents and can compromise clinical response. Over 20 antibodies currently on the market and over 100 drug candidates are currently in clinical trials; all therapeutic antibodies are showing some level of immunogenicity, and although it has been reduced with the advent of antibodies including human sequences, or even humanised antibodies, this concern will not be totally eradicated. Whereas the actual anti-drug response can only be addressed during clinical development or post-marketing, the industry and the regulatory instances are facing a challenge to develop accurate procedures for the assessment of immunogenicity related to antibody therapeutics, addressing both the likelihood and the severity of the drug-related immunogenicity. This review will discuss the multiple factors that can contribute to a potential immunogenicity of protein therapeutics patient/disease related, as well as related to the drug itself, and the strategies to identify anti-drug antibodies, both in clinical and non clinical assays.
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