title: Reducing risk, improving outcomes: bioengineering less immunogenic protein therapeutics.
abstract: One of the great surprises of the biologics revolution has been the discovery that recombinant human proteins, including monoclonals of human origin, can cause immune responses when administered to immune-competent subjects. Preclinical and clinical evaluations of the potential immunogenicity of biologics have been primarily focused on humoral immune responses and as a result, the critical contribution of T cells to the development of anti-monoclonal antibodies (also known as anti-drug antibodies or ADA) has been somewhat overlooked. Recent publications have confirmed the role of effector T cells and begun to explore the role of regulatory T cells in the development of anti-drug antibodies. This review will focus on the role of T-cell-dependent (Td) immunogenicity assessment in the preclinical and clinical phases of drug development and summarize new data on regulatory T-cell epitopes contained in the Fc and CH1 domains of IgG. Recommendations for Td immunogenicity screening and assessment provided in this article may contribute to the development of safer protein-based drugs for human use.
authors.affiliation: EpiVax, Inc., Providence, RI 02903, USA. AnnieD@EpiVax.com
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.forename: William
authors.initials: W
authors.lastname: Martin
mesh_terms: D002626:Chemistry, Pharmaceutical; D006801:Humans; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins