Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy.
10.1007/s13238-017-0433-3
- Author:
Yusuke MIMURA
1
;
Toshihiko KATOH
2
;
Radka SALDOVA
3
;
Roisin O'FLAHERTY
3
;
Tomonori IZUMI
4
;
Yuka MIMURA-KIMURA
5
;
Toshiaki UTSUNOMIYA
5
;
Yoichi MIZUKAMI
6
;
Kenji YAMAMOTO
7
;
Tsuneo MATSUMOTO
5
;
Pauline M RUDD
3
Author Information
1. Department of Clinical Research, NHO Yamaguchi-Ube Medical Center, 685 Higashi-Kiwa, Ube, 755-0241, Japan. mimuray66@outlook.jp.
2. Laboratory of Molecular Biology and Bioresponse, Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kitashirakawa, Oiwake-Cho, Sakyo-Ku, Kyoto, 606-8502, Japan.
3. NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Mount Merrion, Blackrock, Dublin 4, Ireland.
4. Center for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube, 755-8505, Japan.
5. Department of Clinical Research, NHO Yamaguchi-Ube Medical Center, 685 Higashi-Kiwa, Ube, 755-0241, Japan.
6. Center for Gene Research, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, 755-8505, Japan.
7. Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, 1-308 Suematsu, Nonoichi, Ishikawa, 921-8836, Japan.
- Publication Type:Journal Article
- Keywords:
chemoenzymatic glycoengineering;
crystal structure;
endoglycosidase;
fucose;
glycosylation;
intravenous immunoglobulin;
sialic acid;
transglycosylation;
ultra performance liquid chromatography
- MeSH:
Animals;
Antibodies, Monoclonal;
adverse effects;
pharmacokinetics;
therapeutic use;
Glycosylation;
Humans;
Immunoglobulin G;
chemistry;
metabolism;
Protein Engineering;
methods;
Receptors, Fc;
chemistry;
metabolism;
Treatment Outcome
- From:
Protein & Cell
2018;9(1):47-62
- CountryChina
- Language:English
-
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.
