Mimura, Yusuke and Katoh, Toshihiko and Saldova, Radka and O'Flaherty, Roisin and Izumi, Tomonori and Mimura-Kimura, Yuka and Utsunomiya, Toshiaki and Mizukami, Yoichi and Yamamoto, Kenji and Matsumoto, Tsuneo and Rudd, Pauline M. (2018) Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy. Protein and Cell, 9 (1). pp. 47-62. ISSN 1674-800X

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Abstract

Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex-type oligosaccharide attached to Asn297 of the Fc is essential for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that generate structural heterogeneity (glycoforms) exhibit unique biological activities. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for the development and quality control of therapeutic antibodies, and glycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosylation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibilities for the design of novel antibody therapeutics. Furthermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosynthases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety, functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.

Item Type:	Article
Keywords:	chemoenzymatic glycoengineering; crystal structure; endoglycosidase; fucose; glycosylation; intravenous immunoglobulin; sialic acid; transglycosylation; ultra performance; liquid chromatography;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	15048
Identification Number:	https://doi.org/10.1007/s13238-017-0433-3
Depositing User:	Roisin O'Flaherty
Date Deposited:	22 Nov 2021 15:14
Journal or Publication Title:	Protein and Cell
Publisher:	SpringerOpen
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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