Glycoprofiling effects of media additives on IgG produced by CHO cells in fed-batch bioreactors

Helene Faustrup Kildegaard, Yuzhou Fan, Jette Wagtberg Sen, Bo Larsen, Mikael Rørdam Andersen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Therapeutic monoclonal antibodies (mAbs) are mainly produced by heterogonous expression in Chinese hamster ovary (CHO) cells. The glycosylation profile of the mAbs has major impact on the efficacy and safety of the drug and is therefore an important parameter to control during production. In this study, the effect on IgG N-glycosylation from feeding CHO cells with eight glycosylation precursors during cultivation was investigated. The study was conducted in fed-batch mode in bioreactors with biological replicates to obtain highly controlled and comparable conditions. We assessed charge heterogeneity and glycosylation patterns of IgG. None of the eight feed additives caused statistically significant changes to cell growth or IgG productivity, compared to controls. However, the addition of 20 mM galactose did result in a reproducible increase of galactosylated IgG from 14% to 25%. On the other hand, addition of 20 mM N-acetyl-D-glucosamine (GlcNAc) reduced relative abundance of galactosylated IgG by 4%. Additionally, supplementation with 10mM mannose slightly reduced GlcNAc occupancy of IgG. Overall, comparing the effects of IgG glycosylation, by supplementing the cell culture medium with glycosylation precursors during cultivation, revealed an application of these glycosylation precursors for modulating N-glycosylation of IgG.
Original languageEnglish
JournalBiotechnology and Bioengineering (Print)
Volume113
Issue number2
Pages (from-to)359-366
Number of pages8
ISSN0006-3592
DOIs
Publication statusPublished - 2016

Keywords

  • Glycosylation
  • Chinese hamster ovary cells
  • Fed-batch
  • IgG
  • Medium additives

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