A semi-empirical glycosylation model of a camelid monoclonal antibody under hypothermia cell culture conditions

The impact of cell culture environment on the glycan distribution of a monoclonal antibody (mAb) has been investigated through a combination of experiments and modeling. A newly developed CHO DUXB cell line was cultivated at two levels of initial Glutamine (Gln) concentrations (0, 4 mM) and incubati...

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Bibliographic Details
Published in:Journal of industrial microbiology & biotechnology 2017-07, Vol.44 (7), p.1005-1020
Main Authors: Aghamohseni, Hengameh, Spearman, Maureen, Ohadi, Kaveh, Braasch, Katrin, Moo-Young, Murray, Butler, Michael, Budman, Hector M.
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - metabolism
Biochemistry
Bioinformatics
Biomedical and Life Sciences
Biotechnology
Camelidae
Cell culture
Cell Culture and Bioengineering - Original Paper
Cell Culture Techniques
Cell Proliferation
Cells, Cultured
Cellular biology
CHO Cells
Cold Temperature
Correlation
Cricetulus
Environmental impact
Fermentation
Genetic Engineering
Glutamine
Glutamine - metabolism
Glycan
Glycosylation
Hypothermia
Inorganic Chemistry
Life Sciences
Mathematical models
Microbiology
Models, Biological
Monoclonal antibodies
Nucleotides
Polysaccharides - metabolism
Sugar
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Summary:The impact of cell culture environment on the glycan distribution of a monoclonal antibody (mAb) has been investigated through a combination of experiments and modeling. A newly developed CHO DUXB cell line was cultivated at two levels of initial Glutamine (Gln) concentrations (0, 4 mM) and incubation temperatures of (33 and 37 °C) in batch operation mode. Hypothermia was applied either through the entire culture duration or only during the post-exponential phase. Beyond reducing cell growth and increasing productivity, hypothermia significantly altered the galactosylation index profiles as compared to control conditions. A novel semi-empirical dynamic model was proposed for elucidating the connections between the extracellular cell culture conditions to galactosylation index. The developed model is based on a simplified balance of nucleotides sugars and on the correlation between sugars’ levels to the galactosylation index (GI). The model predictions were found to be in a good agreement with the experimental data. The proposed empirical model is expected to be useful for controlling the glycoprofiles by manipulating culture conditions.
ISSN:1367-5435
1476-5535
DOI:10.1007/s10295-017-1926-z