Glycosylation engineering of therapeutic IgG antibodies： challenges for the safety, functionality and efficacy

作     者：Yusuke Mimura Toshihiko Katoh Radka Saldova Roisin O'Flaherty Tomonori Izumi Yuka Mimura-Kimura Toshiaki Utsunomiya Yoichi Mizukami Kenji Yamamoto Tsuneo Matsumoto Pauline M. Rudd 

作者机构：Department of Clinical Research NHO Yamaguchi-Ube Medical Center 685 Higashi-Kiwa Ube 755-0241 Japan Laboratory of Molecular Biology and Bioresponse Division of Integrated Life Science Graduate School of Biostudies KyotoUniversity Kitashirakawa Oiwake-Cho Sakyo-Ku Kyoto 606-8502 Japan NIBRT GlycoScience Group National Institute for Bioprocessing Research and Training Mount Merrion Blackrock Dublin 4Ireland Center for Regenerative Medicine Yamaguchi University Graduate School of Medicine 1-1-1 Minami Kogushi Ube 755-8505 Japan Center for Gene Research Yamaguchi University 1-1-1 Minami-Kogushi Ube 755-8505 Japan Research Institute for Bioresources and Biotechnology Ishikawa Prefectural University 1-308 Suematsu Nonoichi Ishikawa 921-8836 Japan 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2018年第9卷第1期

页      面：47-62页

核心收录：

学科分类：090603[农学-临床兽医学] 0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 090602[农学-预防兽医学] 1002[医学-临床医学] 09[农学] 0906[农学-兽医学] 0703[理学-化学] 0836[工学-生物工程] 

基　　金：supported by JSPS KAKENHI (Y. M.) the Science Foundation Ireland Starting Investigator Research grant (SFI SIRG) (R. S.) EU FP7 program HighGlycan (R. O.) 

主　　题：chemoenzymatic glycoengineering crysta structure endoglycosidase fucose glycosylation,intravenous immunoglobulin sialic acid transglycosylation,ultra performance liquid chromatography 

摘      要：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 essen- tial for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that gen- erate structural heterogeneity （glycoforms） exhibit unique biological activities. Hence, efficient and quan- titative glycan analysis techniques have been increas- ingly important for the development and quality control of therapeutic antibodies, and g｜ycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosy- lation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibili- ties for the design of novel antibody therapeutics. Fur- thermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosyn- thases 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.