Model-based optimization of antibody galactosylation in CHO cell culture
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.
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When galactose is supplemented, carbon flux can be redirected towards central energy metabolism, reducing reliance on glucose as the primary carbon and energy source.
“When galactose is supplemented, carbon flux can be redirected towards central energy metabolism, reducing reliance on glucose as the primary carbon and energy source.”
From Soft sensing of intracellular states for CHO cell bioprocessing with Ensemble Kalman Filters (2026) · cites this paper as [25]
Model parameters were identified using 5 fed-batch experiments reported by Kotidis et al. (2019), generated from an IgG-producing CHO-T127 cell line operated under different galactose and uridine supplementation strategies.
“Model parameters were identified using 5 fed-batch experiments reported by Kotidis et al. (2019), generated from an IgG-producing CHO-T127 cell line operated under different galactose and uridine supplementation strategies [25].”
From Soft sensing of intracellular states for CHO cell bioprocessing with Ensemble Kalman Filters (2026) · cites this paper as [25]
NSDs are synthesised intracellularly from extracellular metabolites such as glucose, glutamine, galactose, and uridine through a sequence of cytosolic enzymatic reactions, and are subsequently consumed in the Golgi apparatus during glycosylation.
“NSDs are synthesised intracellularly from extracellular metabolites such as glucose, glutamine, galactose, and uridine through a sequence of cytosolic enzymatic reactions, and are subsequently consumed in the Golgi apparatus during glycosylation [20,21,25].”
From Soft sensing of intracellular states for CHO cell bioprocessing with Ensemble Kalman Filters (2026) · cites this paper as [25]
Cites
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How does mild hypothermia affect monoclonal antibody glycosylation?
Sou, S. N., Sellick, C., Lee, K., Mason, A., Kyriakopoulos, S., Polizzi, K. M., & Kontoravdi, C. (2015) · Biotechnology and Bioengineering · doi:10.1002/bit.25524 · Cited by 107 · see citing works
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Continuous integrated manufacturing for biopharmaceuticals: A new paradigm or an empty promise?
Rathore, A. S., Thakur, G., & Kateja, N. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28235 · Cited by 41 · see citing works
mAb Production Modeling and Design Space Evaluation Including Glycosylation Process
Yang, O., & Ierapetritou, M. (2021) · Processes · doi:10.3390/pr9020324 · Cited by 26 · see citing works
Soft sensing of intracellular states for CHO cell bioprocessing with Ensemble Kalman Filters
Yu, L., del Rio Chanona, A., & Kontoravdi, C. (2026) · Journal of Process Control · doi:10.1016/j.jprocont.2026.103875
Self-citation
- Authors
- Kotidis, P., Jedrzejewski, P., Sou, S. N., Sellick, C., Polizzi, K., del Val, I. J., & Kontoravdi, C.
- Affiliations
- Imperial College London (GB)
- Kymab (United Kingdom) (GB)
- School of Chemical & Bioprocess Engineering University College Dublin Ireland
- Corresponding author
- Kontoravdi, Cleo
- ORCID
- Venue
- Biotechnology and Bioengineering
- Publisher
- Wiley
- Published
- 2019-03-21
- Volume
- 116
- Issue
- 7
- Pages
- 1612-1626
- ISSN
- 0006-3592 (ISSN-L)
- 1097-0290
- OpenAlex
- W2918163347
- Cited by
- 90
- References
- 3
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 16 · 2023: 14 · 2022: 8 · 2021: 15 · 2020: 10 · 2019: 4
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biotechnology and Bioengineering (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/I017011/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- CHO cell culture, galactose feeding, antibody productivity, process optimization, quality by design, bioprocess modeling
- MeSH terms
- Animals, Antibodies, Monoclonal, Cricetulus, Glycosylation, Models, Biological, CHO Cells
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