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

Frances Rocamora; Angelo G Peralta; Seunghyeon Shin; James Sorrentino; Mina Ying Min Wu; Eric A Toth; Thomas R Fuerst; Nathan E Lewis

doi:10.1016/j.biotechadv.2023.108206

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.

Authors

Frances Rocamora¹, Angelo G Peralta¹, Seunghyeon Shin¹, James Sorrentino¹, Mina Ying Min Wu², Eric A Toth³, Thomas R Fuerst⁴, Nathan E Lewis⁵

Affiliations

¹ Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
² Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
³ Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
⁴ Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
⁵ Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: nlewisres@ucsd.edu.

PMID: 37354999
DOI: 10.1016/j.biotechadv.2023.108206

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

Grants and funding

R35 GM119850/GM/NIGMS NIH HHS/United States