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

• Published in: Biotechnology advances Vol. 67; p. 108206
• Main Authors: Rocamora, Frances, Peralta, Angelo G., Shin, Seunghyeon, Sorrentino, James, Wu, Mina Ying Min, Toth, Eric A., Fuerst, Thomas R., Lewis, Nathan E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.10.2023
• Subjects: Antibodies, Monoclonal - chemistry; Biologic; Cell- and Tissue-Based Therapy; Cell-based therapy; Gene therapy; Glycoengineering; Glycosylation; Humans; Monoclonal antibody; Neoplasms - drug therapy; Neoplasms - therapy; Polysaccharides - chemistry; Therapeutic protein; Therapeutic protein; Glycoengineering; Cell-based therapy; Glycosylation; Monoclonal antibody; Gene therapy; Biologic
• ISSN: 0734-9750; 1873-1899; 1873-1899
• DOI: 10.1016/j.biotechadv.2023.108206

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. •Glycosylation is a common feature of protein-based drugs and impacts their stability, safety, and therapeutic efficacy.•Manipulating glycan heterogeneity is a powerful in developing products with optimal physical and biological properties.•Glycoengineering can improve the efficacy of newer biologics such as T cell-basedand oligonucleotide-based therapeutics.