Structural Elucidation of Chemical and Post-translational Modifications of Monoclonal Antibodies

Published

October 15, 2015

Author(s)

Wenzhou Li, James L. Kerwin, John E. Schiel, Catherine A. Mouchahoir, Darryl Davis, Andrew Mahan, Sabrina A. Benchaar

Abstract

Therapeutic monoclonal antibodies (mAbs), a rapidly growing class of therapeutic drugs, present a daunting challenge for structural characterization. They are heterodimers of separate light and heavy chains comprising over 1200 amino acid residues. During cellular production as well as during processing and storage, the primary amino acid sequence may be modified through post-translational or chemical processes, and these modifications can affect biological activity, half-life and immunogenicity. Beginning with basic research and proceeding through the various steps of production and formulation, post-translational and chemical modifications (PTMs) must be discovered, tracked, and evaluated for quality, safety, and efficacy. A brief review of the more common modifications encountered during development is presented, with emphasis on those identified on the reference mAb provided by the National Institute of Standards and Technology (NIST). Current and future promising approaches utilizing mass spectrometric and complementary techniques for structural characterization of mAbs are discussed. Many of the aforementioned techniques were used in the characterization of the NIST mAb Reference Material, the results of which are summarized in this chapter.

Citation

Current, State of the Art, and Emerging Technologies for the Analysis of Monoclonal Antibodies

Publisher Info

ACS Publications, Washington, DC

Pub Type

Books

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DOI Link

Keywords

NIST mAb, biopharmaceutical characterization, monoclonal antibody, post-translational modification, peptide mapping, forced degradation

Citation

Li, W. , Kerwin, J. , Schiel, J. , Mouchahoir, C. , Davis, D. , Mahan, A. and Benchaar, S. (2015), Structural Elucidation of Chemical and Post-translational Modifications of Monoclonal Antibodies, ACS Publications, Washington, DC, [online], https://doi.org/10.1021/bk-2015-1201.ch003 (Accessed October 10, 2024)