T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.

Frontiers in Immunology
Vibha JawaAnne S De Groot

Abstract

Immune responses to protein and peptide drugs can alter or reduce their efficacy and may be associated with adverse effects. While anti-drug antibodies (ADA) are a standard clinical measure of protein therapeutic immunogenicity, T cell epitopes in the primary sequences of these drugs are the key drivers or modulators of ADA response, depending on the type of T cell response that is stimulated (e.g., T helper or Regulatory T cells, respectively). In a previous publication on T cell-dependent immunogenicity of biotherapeutics, we addressed mitigation efforts such as identifying and reducing the presence of T cell epitopes or T cell response to protein therapeutics prior to further development of the protein therapeutic for clinical use. Over the past 5 years, greater insight into the role of regulatory T cell epitopes and the conservation of T cell epitopes with self (beyond germline) has improved the preclinical assessment of immunogenic potential. In addition, impurities contained in therapeutic drug formulations such as host cell proteins have also attracted attention and become the focus of novel risk assessment methods. Target effects have come into focus, given the emergence of protein and peptide drugs that target immune r...Continue Reading

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Citations

Nov 22, 2020·Journal of Pharmaceutical Sciences·Adam GrabarekWim Jiskoot
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Methods Mentioned

BETA
glycosylation
fluorescence spectroscopy
flow cytometry
immunoprecipitation
Assay

Software Mentioned

JanusMatrix
MAPPS
Tregitope
QSP
ISPRI
ISPRI Toolkit
Mass Spec

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