title: T cell epitope: friend or foe? Immunogenicity of biologics in context.
abstract: Like vaccines, biologic proteins can be very immunogenic for reasons including route of administration, dose frequency and the underlying antigenicity of the therapeutic protein. Because the impact of immunogenicity can be quite severe, regulatory agencies are developing risk-based guidelines for immunogenicity screening. T cell epitopes are at the root of the immunogenicity issue. Through their presentation to T cells, they activate the process of anti-drug antibody development. Preclinical screening for T cell epitopes can be performed in silico, followed by in vitro and in vivo validation. Importantly, screening for immunogenicity is complicated by the discovery of regulatory T cell epitopes, which suggests that immunogenicity testing must now take regulatory T cells into consideration. In this review, we address the application of computational tools for preclinical immunogenicity assessment, the implication of the discovery of regulatory T cell epitopes, and experimental validation of those assessments.
authors.affiliation: EpiVax, Providence, RI 02903, USA.
authors.forename: Constanze A
authors.initials: CA
authors.lastname: Weber
authors.forename: Preema J
authors.initials: PJ
authors.lastname: Mehta
authors.forename: Matt
authors.initials: M
authors.lastname: Ardito
authors.forename: Lenny
authors.initials: L
authors.lastname: Moise
authors.forename: Bill
authors.initials: B
authors.lastname: Martin
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001688:Biological Products / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001688:Biological Products; D018984:Epitopes, T-Lymphocyte