Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies

Biotechnol Adv. 2023 Oct:67:108206. doi: 10.1016/j.biotechadv.2023.108206. Epub 2023 Jun 22.

Abstract

Over recent decades, therapeutic proteins have had widespread success in treating a myriad of diseases. Glycosylation, a near universal feature of this class of drugs, is a critical quality attribute that significantly influences the physical properties, safety profile and biological activity of therapeutic proteins. Optimizing protein glycosylation, therefore, offers an important avenue to developing more efficacious therapies. In this review, we discuss specific examples of how variations in glycan structure and glycoengineering impacts the stability, safety, and clinical efficacy of protein-based drugs that are already in the market as well as those that are still in preclinical development. We also highlight the impact of glycosylation on next generation biologics such as T cell-based cancer therapy and gene therapy.

Keywords: Biologic; Cell-based therapy; Gene therapy; Glycoengineering; Glycosylation; Monoclonal antibody; Therapeutic protein.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal* / chemistry
  • Cell- and Tissue-Based Therapy
  • Glycosylation
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / therapy
  • Polysaccharides / chemistry

Substances

  • Antibodies, Monoclonal
  • Polysaccharides