title: A semi-empirical glycosylation model of a camelid monoclonal antibody under hypothermia cell culture conditions.
abstract: 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.
authors.affiliation: Faculty of Engineering, Chemical Engineering Department, University of Waterloo, E6 Building, Room 3012, 200 University Avenue West, Waterloo, ON, N2L 3G1, Canada.
authors.forename: Hengameh
authors.initials: H
authors.lastname: Aghamohseni
authors.affiliation: Microbiology Department, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Maureen
authors.initials: M
authors.lastname: Spearman
authors.affiliation: Faculty of Engineering, Chemical Engineering Department, University of Waterloo, E6 Building, Room 3012, 200 University Avenue West, Waterloo, ON, N2L 3G1, Canada.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Ohadi
authors.affiliation: Microbiology Department, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Katrin
authors.initials: K
authors.lastname: Braasch
authors.affiliation: Faculty of Engineering, Chemical Engineering Department, University of Waterloo, E6 Building, Room 3012, 200 University Avenue West, Waterloo, ON, N2L 3G1, Canada.
authors.forename: Murray
authors.initials: M
authors.lastname: Moo-Young
authors.affiliation: Microbiology Department, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Butler
authors.affiliation: Faculty of Engineering, Chemical Engineering Department, University of Waterloo, E6 Building, Room 3012, 200 University Avenue West, Waterloo, ON, N2L 3G1, Canada. hbudman@uwaterloo.ca.
authors.forename: Hector M
authors.initials: HM
authors.lastname: Budman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D016466:CHO Cells; D000071194:Camelidae; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D003080:Cold Temperature; D003412:Cricetulus; D005973:Glutamine / Q000378:metabolism; D006031:Glycosylation; D008954:Models, Biological; D011134:Polysaccharides / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D011134:Polysaccharides; D005973:Glutamine
keywords: Chinese hamster ovary cells; Glycosylation; Hypothermia; Mathematical modeling; Monoclonal antibody