TY - JOUR
T1 - Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors
AU - Li, Shasha
AU - McCraw, Alex J
AU - Gardner, Richard A
AU - Spencer, Daniel I R
AU - Karagiannis, Sophia N
AU - Wagner, Gerd K
N1 - Funding Information:
The authors acknowledge support by Cancer Research UK King?s Health Partners Centre at King?s College London (C604/A25135); the Medical Research Council (MR/L023091/1); CR Funding: UK//NIHR The in authors England/DoH acknowledge for support Scotland, by Wales Cancer and Research Northern UK King?s Ireland Health Experimental Partners Cancer Centre at Medicine King?s Centre College (C10355/A15587); London (C604/A25135); Breast Cancer the Now Medical (147; Research KCL-BCN-Q3); Council the (MR/L023091/1); Guy?s and St Thomas? CR UK//NIHR Foundation in Trust England/DoH Charity Melanoma for Scotland, Special Wales Fund and (SPF573); Northern Cancer Ireland Research Experimental UK (C30122/A11527; Cancer Medicine C30122/A15774). Centre (C10355/A15587); The research Breast was supported Cancer Now by the (147; National KCL-BCN-Q3); Institute for the Health Guy?s Research and St Thomas? Biomedical Research FoundationTrust Trust Centre Charity based Melanoma at Guy?s Special and St Fund Thomas? (SPF573); NHS Foundation Cancer Research Trust UK and (C30122/A11527; King?s College C30122/A15774). The research was supported by the National Institute for Health Research Biomedical Research Centre based at Guy?s and St Thomas? NHS Foundation Trust and King?s College London (IS-BRC-1215-20006). S.L is the recipient of a studentship from the Chinese Scholarship Council. A.J.M. is the recipient of a MRC CASE studentship, co-funded by Ludger Ltd. The authors London (IS-BRC-1215-20006). S.L is the recipient of a studentship from the Chinese Scholarship are solely responsible for study design, data collection, analysis, decision to publish, and preparation Council. A.J.M. is the recipient of a MRC CASE studentship, co-funded by Ludger Ltd. The authors Centre Charity based Melanoma at Guy?s Special and St Fund Thomas? (SPF573); NHS Foundation Cancer Research Trust UK and (C30122/A11527; King?s College C30122/A15774). The research was supported by the National Institute for Health Research Biomedical Research Centre based at Guy?s and St Thomas? NHS Foundation Trust and King?s College London (IS-BRC-1215-20006). S.L is the recipient of a studentship from the Chinese Scholarship Council. A.J.M. is the recipient of a MRC CASE studentship, co-funded by Ludger Ltd. The authors London (IS-BRC-1215-20006). S.L is the recipient of a studentship from the Chinese Scholarship are solely responsible for study design, data collection, analysis, decision to publish, and preparation Council. A.J.M. is the recipient of a MRC CASE studentship, co-funded by Ludger Ltd. The authorsof the manuscript. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.
Funding Information:
Author Contributions: Conceptualization, S.N.K. and G.K.W.; original draft preparation, A.J.M., S.L. and G.K.W.; review and editing, R.A.G. and D.I.R.S. All authors contributed to the review and editing of the manuscript. All authors have read and agreed to the published version of the manu-script.Funding: The authors acknowledge support by Cancer Research UK King’s Health Partners Centre at King’s College London (C604/A25135); the Medical Research Council (MR/L023091/1); CR Funding: The authors acknowledge support by Cancer Research UK King’s Health Partners Centre at King’s College London (C604/A25135); the Medical Research Council (MR/L023091/1); CR UK//NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587); Breast Cancer Now (147; KCL-BCN-Q3); the Guy’s and St Thomas’ Foundation Trust Charity Melanoma Special Fund (SPF573); Cancer Research UK (C30122/A11527; ical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College C30122/A15774). The research was supported by the National Institute for Health Research Biomed-London (IS-BRC-1215-20006). S.L is the recipient of a studentship from the Chinese Scholarship ical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College Council. A.J.M. is the recipient of a MRC CASE studentship, co-funded by Ludger Ltd. The authors London (IS-BRC-1215-20006). S.L is the recipient of a studentship from the Chinese Scholarship are solely responsible for study design, data collection, analysis, decision to publish, and preparation Council. A.J.M. is the recipient of a MRC CASE studentship, co-funded by Ludger Ltd. The authors
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/4
Y1 - 2021/11/4
N2 - Monoclonal antibodies (mAbs) are one of the cornerstones of modern medicine, across an increasing range of therapeutic areas. All therapeutic mAbs are glycoproteins, i.e., their polypeptide chain is decorated with glycans, oligosaccharides of extraordinary structural diversity. The presence, absence, and composition of these glycans can have a profound effect on the pharmacodynamic and pharmacokinetic profile of individual mAbs. Approaches for the glycoengineering of therapeutic mAbs-the manipulation and optimisation of mAb glycan structures-are therefore of great interest from a technological, therapeutic, and regulatory perspective. In this review, we provide a brief introduction to the effects of glycosylation on the biological and pharmacological functions of the five classes of immunoglobulins (IgG, IgE, IgA, IgM and IgD) that form the backbone of all current clinical and experimental mAbs, including an overview of common mAb expression systems. We review selected examples for the use of small molecule inhibitors of glycan biosynthesis for mAb glycoengineering, we discuss the potential advantages and challenges of this approach, and we outline potential future applications. The main aim of the review is to showcase the expanding chemical toolbox that is becoming available for mAb glycoengineering to the biology and biotechnology community.
AB - Monoclonal antibodies (mAbs) are one of the cornerstones of modern medicine, across an increasing range of therapeutic areas. All therapeutic mAbs are glycoproteins, i.e., their polypeptide chain is decorated with glycans, oligosaccharides of extraordinary structural diversity. The presence, absence, and composition of these glycans can have a profound effect on the pharmacodynamic and pharmacokinetic profile of individual mAbs. Approaches for the glycoengineering of therapeutic mAbs-the manipulation and optimisation of mAb glycan structures-are therefore of great interest from a technological, therapeutic, and regulatory perspective. In this review, we provide a brief introduction to the effects of glycosylation on the biological and pharmacological functions of the five classes of immunoglobulins (IgG, IgE, IgA, IgM and IgD) that form the backbone of all current clinical and experimental mAbs, including an overview of common mAb expression systems. We review selected examples for the use of small molecule inhibitors of glycan biosynthesis for mAb glycoengineering, we discuss the potential advantages and challenges of this approach, and we outline potential future applications. The main aim of the review is to showcase the expanding chemical toolbox that is becoming available for mAb glycoengineering to the biology and biotechnology community.
UR - http://www.scopus.com/inward/record.url?scp=85118956986&partnerID=8YFLogxK
U2 - 10.3390/antib10040044
DO - 10.3390/antib10040044
M3 - Article
C2 - 34842612
SN - 2073-4468
VL - 10
JO - Antibodies (Basel, Switzerland)
JF - Antibodies (Basel, Switzerland)
IS - 4
M1 - 44
ER -