Cargando…

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

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 he...

Descripción completa

Detalles Bibliográficos
Autores principales: Mimura, Yusuke, Katoh, Toshihiko, Saldova, Radka, O’Flaherty, Roisin, Izumi, Tomonori, Mimura-Kimura, Yuka, Utsunomiya, Toshiaki, Mizukami, Yoichi, Yamamoto, Kenji, Matsumoto, Tsuneo, Rudd, Pauline M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Higher Education Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777974/
https://www.ncbi.nlm.nih.gov/pubmed/28597152
http://dx.doi.org/10.1007/s13238-017-0433-3
_version_ 1783294264005885952
author Mimura, Yusuke
Katoh, Toshihiko
Saldova, Radka
O’Flaherty, Roisin
Izumi, Tomonori
Mimura-Kimura, Yuka
Utsunomiya, Toshiaki
Mizukami, Yoichi
Yamamoto, Kenji
Matsumoto, Tsuneo
Rudd, Pauline M.
author_facet Mimura, Yusuke
Katoh, Toshihiko
Saldova, Radka
O’Flaherty, Roisin
Izumi, Tomonori
Mimura-Kimura, Yuka
Utsunomiya, Toshiaki
Mizukami, Yoichi
Yamamoto, Kenji
Matsumoto, Tsuneo
Rudd, Pauline M.
author_sort Mimura, Yusuke
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5777974
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Higher Education Press
record_format MEDLINE/PubMed
spelling pubmed-57779742018-02-01 Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy Mimura, Yusuke Katoh, Toshihiko Saldova, Radka O’Flaherty, Roisin Izumi, Tomonori Mimura-Kimura, Yuka Utsunomiya, Toshiaki Mizukami, Yoichi Yamamoto, Kenji Matsumoto, Tsuneo Rudd, Pauline M. Protein Cell Review 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. Higher Education Press 2017-06-08 2018-01 /pmc/articles/PMC5777974/ /pubmed/28597152 http://dx.doi.org/10.1007/s13238-017-0433-3 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Mimura, Yusuke
Katoh, Toshihiko
Saldova, Radka
O’Flaherty, Roisin
Izumi, Tomonori
Mimura-Kimura, Yuka
Utsunomiya, Toshiaki
Mizukami, Yoichi
Yamamoto, Kenji
Matsumoto, Tsuneo
Rudd, Pauline M.
Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy
title Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy
title_full Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy
title_fullStr Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy
title_full_unstemmed Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy
title_short Glycosylation engineering of therapeutic IgG antibodies: challenges for the safety, functionality and efficacy
title_sort glycosylation engineering of therapeutic igg antibodies: challenges for the safety, functionality and efficacy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777974/
https://www.ncbi.nlm.nih.gov/pubmed/28597152
http://dx.doi.org/10.1007/s13238-017-0433-3
work_keys_str_mv AT mimurayusuke glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT katohtoshihiko glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT saldovaradka glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT oflahertyroisin glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT izumitomonori glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT mimurakimurayuka glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT utsunomiyatoshiaki glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT mizukamiyoichi glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT yamamotokenji glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT matsumototsuneo glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy
AT ruddpaulinem glycosylationengineeringoftherapeuticiggantibodieschallengesforthesafetyfunctionalityandefficacy