AAPS Blog: That Was Then, This is Now: Trends in Immunogenicity and Tolerance
By, Anne De Groot, M.D., professor and director at the University of Rhode Island’s Institute for Immunology and Informatics.

Sometimes handlebar mustaches are in, and sometimes, they are very, very out! The world of fashion is well known for its “emerging trends” and well, it seems that trends are also common in preclinical development of protein therapeutics. Ten years ago, anti-drug antibody (ADA) responses to protein therapeutics were the focus of each and every meeting, while aficionados of T cells (with and without handlebar mustaches) made time to talk about their favorite topic over lunch. At that time, few but the bravest would bring up the concept of doing T cell epitope- focused immunoinformatics analysis of biologic proteins in the preclinical phase of drug development. The T cell-driven immune response, as a contributor to protein immunogenicity, was definitely a “fringe” concept.

That was then, and this is now. As a group, biologics developers have broadened their horizons over the past 10 years, to consider the implications of T cell epitopes in the evaluation of protein therapeutic immunogenicity. Now, such concepts as inducing tolerance, screening for T cell epitope content, or even removing T cell epitopes to lower protein immunogenicity (deimmunization) that might once have been considered avant garde are considered de rigeur. Protein drug developers are now taking a broader view of preclinical immunogenicity screening, leading to changes in the way biotherapeutics are developed and advances in our ability to reduce protein immunogenicity that will have a significant impact on human health.

We are well past handlebar mustaches and bushy side-burns. Now, the ability of immunoinformatics tools to predict and reduce immunogenicity of a potential protein therapeutic is well recognized, and drug developers ….. FULL POST HERE.