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Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist’s Perspective

Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors

Medical Biology Centre, School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK
St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, 9th Floor Tower Wing, Guy’s Hospital, London SE1 9RT, UK
Ludger, Ltd., Culham Science Centre, Abingdon, Oxfordshire OX14 3EB, UK
Breast Cancer Now Research Unit, Guy’s Cancer Centre, School of Cancer & Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK
Author to whom correspondence should be addressed.
Academic Editor: Ohad Mazor
Received: 27 September 2021 / Revised: 27 October 2021 / Accepted: 27 October 2021 / Published: 4 November 2021
(This article belongs to the Special Issue Antibody Engineering for Cancer Immunotherapy)
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. View Full-Text
Keywords: antibody; immunoglobulin; glycan; glycoengineering; glycosylation; glycoform; inhibitor; chemical tools antibody; immunoglobulin; glycan; glycoengineering; glycosylation; glycoform; inhibitor; chemical tools
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MDPI and ACS Style

Li, S.; McCraw, A.J.; Gardner, R.A.; Spencer, D.I.R.; Karagiannis, S.N.; Wagner, G.K. Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors. Antibodies 2021, 10, 44.

AMA Style

Li S, McCraw AJ, Gardner RA, Spencer DIR, Karagiannis SN, Wagner GK. Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors. Antibodies. 2021; 10(4):44.

Chicago/Turabian Style

Li, Shasha, Alex J. McCraw, Richard A. Gardner, Daniel I.R. Spencer, Sophia N. Karagiannis, and Gerd K. Wagner. 2021. "Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors" Antibodies 10, no. 4: 44.

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