Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Humanized antibody therapeutics rarely caused anaphylaxis although it was often seen in the introduction of literatures that immunogenicity of biotherapeutics is an important issue because anti-drug antibody (ADA) may cause anaphylaxis. Realistic issues with immunogenicity of antibody therapeutics are vasculitis by drug-ADA immune complex and reduction of efficacy by decreased drug concentration in blood and/or by neutralizing activity of ADA. How can we predict immunogenicity of an antibody therapeutic? Even in vivo tests with “relevant animal species” defined by ICH S6 cannot predict human immunogenicity. Recently increasing IgG formats with modifications from human origin would need checking immunogenicity before clinical trials. In vitro tests for T cell activation, analysis of peptides presented on HLA and other methods were reported to provide useful information. There is a successful example of development of a low immunogenic modified antibody drug for a chronic disease using the information from those assays. Contrary, some human IgG frequently generate ADA in patients. Factors other than amino acid sequences can affect immunogenicity of antibody therapeutics. It is plausible that impurities in drug products has considerable impact on immunogenicity. We here review the method to predict immunogenicity of antibody therapeutics, and discuss how we can know impact of impurities which may be escaped from current screening assays.
