-
148 Accesses
Abstract
The N-glycosylation on therapeutic monoclonal antibodies (mAbs) plays important biological roles such as antibody-dependent cellular cytotoxicity (ADCC) or circulatory half-time in vivo. Although the attached N-glycans are mostly core α1-6-fucosylated biantennary glycans, minor nonhuman N-glycans having N-glycolylneuraminic acid (NeuGc) and Galα1-3Gal epitopes (αGal) have been reported to be present in therapeutic mAbs. Determination of nonhuman N-glycans is important in the evaluation of the mAb characteristics, because the presence of nonhuman N-glycans may affect the safety of mAb products leading to immunogenicity or adverse incident. In this chapter, we present the method for validation of mAbs based on glycan profiles using capillary electrophoresis (CE) with laser-induced fluorescence detection (LIF). The presented method using CE-LIF allows the routine testing to ensure safety and efficacy of the mAb products.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Benchmark Glycan Profile of Therapeutic Monoclonal Antibodies Produced by Mammalian Cell Expression Systems
Explore related subjects
Discover the latest articles, books and news in related subjects, suggested using machine learning.References
Beck A, Bussat MC, Zorn N, Robillard V, Klinguer-Hamour C, Chenu S, Goetsch L, Corvaia N, Van Dorsselaer A, Haeuw JF (2005) Characterization by liquid chromatography combined with mass spectrometry of monoclonal anti-IGF-1 receptor antibodies produced in CHO and NS0 cells. J Chromatogr B Analyt Technol Biomed Life Sci 819:203–218
Beck A, Wagner-Rousset E, Ayoub D, Van Dorsselaer A, Sanglier-Cianferani S (2012) Characterization of therapeutic antibodies and related products. Anal Chem 85:715–736
Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, Murphy BA, Satinover SM, Hosen J, Mauro D et al (2008) Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 358:1109–1117
Joziasse DH, Shaper JH, Jabs EW, Shaper NL (1991) Characterization of an alpha 1–3-galactosyltransferase homologue on human chromosome 12 that is organized as a processed pseudogene. J Biol Chem 266:6991–6998
Kamoda S, Nomura C, Kinoshita M, Nishiura S, Ishikawa R, Kakehi K, Kawasaki N, Hayakawa T (2004) Profiling analysis of oligosaccharides in antibody pharmaceuticals by capillary electrophoresis. J Chromatogr A 1050:211–216
Kamoda S, Ishikawa R, Kakehi K (2006) Capillary electrophoresis with laser-induced fluorescence detection for detailed studies on N-linked oligosaccharide profile of therapeutic recombinant monoclonal antibodies. J Chromatogr A 1133:332–339
Maeda E, Kita S, Kinoshita M, Urakami K, Hayakawa T, Kakehi K (2012) Analysis of nonhuman N-glycans as the minor constituents in recombinant monoclonal antibody pharmaceuticals. Anal Chem 84:2373–2379
Morimoto N, Nakano M, Kinoshita M, Kawabata A, Morita M, Oda Y, Kuroda R, Kakehi K (2001) Specific distribution of sialic acids in animal tissues as examined by LC-ESI-MS after derivatization with 1,2-diamino-4,5-methylenedioxybenzene. Anal Chem 73:5422–5428
Nakamura K, Ariga T, Yahagi T, Miyatake T, Suzuki A, Yamakawa T (1983) Interspecies comparison of muscle gangliosides by two-dimensional thin-layer chromatography. J Biochem 94:1359–1365
Raju TS, Jordan RE (2012) Galactosylation variations in marketed therapeutic antibodies. MAbs 4:385–391
Editor information
Editors and Affiliations
Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
Tamao Endo
Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany
Peter H. Seeberger
Dept. Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Gerald W. Hart
Academia Sinica, Nankang, Taipei, Taiwan
Chi-Huey Wong
Systems Glycobiology Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Wako, Saitama, Japan
Naoyuki Taniguchi
Rights and permissions
Copyright information
© 2014 Springer Japan
About this entry
Cite this entry
Kinoshita, M., Kakehi, K. (2014). Capillary Electrophoresis of Glycans: Validation of Antibody Pharmaceuticals Based on Glycan Profiles. In: Endo, T., Seeberger, P., Hart, G., Wong, CH., Taniguchi, N. (eds) Glycoscience: Biology and Medicine. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54836-2_9-1
Download citation
DOI: https://doi.org/10.1007/978-4-431-54836-2_9-1
Received:
Accepted:
Published:
Publisher Name: Springer, Tokyo
Online ISBN: 978-4-431-54836-2
eBook Packages: Living Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences