Glycobiology Advance Access published online on June 3, 2009
Glycobiology, doi:10.1093/glycob/cwp079
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Review |
Optimal and Consistent Protein Glycosylation in Mammalian Cell Culture
2 Process Sciences Upstream, Technical Operations, Bristol-Myers Squibb Company, East Syracuse, NY 13057
1 To whom correspondence should be addressed: Tel: 315-432-2131; email: zhengjian.li{at}bms.com
Received on April 6, 2009; accepted on June 1, 2009
In the biopharmaceutical industry, mammalian cell culture systems, especially Chinese hamster ovary (CHO) cells, are predominantly used for the production of therapeutic glycoproteins. Glycosylation is a critical protein quality attribute that can modulate the efficacy of a commercial therapeutic glycoprotein. Obtaining a consistent glycoform profile in production is desired due to regulatory concerns because a molecule can be defined by its carbohydrate structures. An optimal profile may involve a spectrum of product glycans that confers a desired therapeutic efficacy, or a homogeneous glycoform profile that can be systemically screened for. Studies have shown some degree of protein glycosylation control in mammalian cell culture, through cellular, media, and process effects. Studies upon our own bioprocesses to produce fusion proteins and monoclonal antibodies have shown an intricate relationship between these variables and the resulting protein quality. Glycosylation optimization will improve therapeutic efficacy and is an ongoing goal for researchers in academia and industry alike. This review will focus on the advancements made in glycosylation control in a manufacturing process, as well as the next steps in understanding and controlling protein glycosylation.
Key words: Protein Glycosylation / Mammalian Cell Culture / Bioprocessing / Protein Quality / Protein therapeutics
3 Present address: Abbott Bioresearch Center, Abbot Laboratories, Worcester, MA 01605