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Clin Immunol. 2009 May;131(2):189-201. doi: 10.1016/j.clim.2009.01.009. Epub 2009 Mar 6.

Reducing risk, improving outcomes: bioengineering less immunogenic protein therapeutics.

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EpiVax, Inc., Providence, RI 02903, USA.


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.

[Indexed for MEDLINE]

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