Model-based optimization of antibody galactosylation in CHO cell culture
File(s)
Author(s)
Type
Journal Article
Abstract
Exerting control over the glycan moieties of antibody therapeutics is highly desirable from a product safety and batch-to-batch consistency perspective. Strategies to improve antibody productivity may compromise quality, while interventions for improving glycoform distribution can adversely affect cell growth and productivity. Process design therefore needs to consider the trade-off between preserving cellular health and productivity while enhancing antibody quality. In this work, we present a modeling platform that quantifies the impact of glycosylation precursor feeding - specifically that of galactose and uridine - on cellular growth, metabolism as well as antibody productivity and glycoform distribution. The platform has been parameterized using an initial training data set yielding an accuracy of ±5% with respect to glycoform distribution. It was then used to design an optimized feeding strategy that enhances the final concentration of galactosylated antibody in the supernatant by over 90% compared with the control without compromising the integral of viable cell density or final antibody titer. This work supports the implementation of Quality by Design towards higher-performing bioprocesses.
Date Issued
2019-07-01
Date Acceptance
2019-02-21
Citation
Biotechnology and Bioengineering, 2019, 116 (7), pp.1612-1626
ISSN
0006-3592
Publisher
Wiley
Start Page
1612
End Page
1626
Journal / Book Title
Biotechnology and Bioengineering
Volume
116
Issue
7
Copyright Statement
© 2019 Wiley Periodicals, Inc. This is the accepted version of the following article: Kotidis, P, Jedrzejewski, P, Sou, SN, et al. Model‐based optimization of antibody galactosylation in CHO cell culture. Biotechnology and Bioengineering. 2019; 1– 15., which has been published in final form at https://dx.doi.org/10.1002/bit.26960
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30802295
Grant Number
BB/I017011/1
Subjects
Chinese hamster ovary (CHO) cells
antibody glycosylation
galactosylation
mathematical modeling
nucleotide sugars
process optimization
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-02-25