Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors

Shasha Li, Alex J. McCraw, Richard A. Gardner, Daniel I.R. Spencer, Sophia N. Karagiannis, Gerd K. Wagner*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

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.
Original languageEnglish
Article number44
JournalAntibodies
Volume10
Issue number4
Early online date04 Nov 2021
DOIs
Publication statusEarly online date - 04 Nov 2021

Keywords

  • antibody
  • immunoglobulin
  • glycan
  • glycoengineering
  • glycosylation
  • glycoform
  • inhibitor
  • chemical tools

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