Development and analysis of a mathematical model for antibody-producing GS-NS0 cells under normal and hyperosmotic culture conditions.
The GS-NS0 cell line is industrially important and is currently used for the large-scale production of several therapeutic monoclonal antibodies. A novel hybrid model, consisting of both unstructured and structured elements, has been developed to describe cell growth and death, metabolism, and antibody production in the GS-NS0 system under normal culture conditions. A comparison between the hybrid model and a large-scale single-cell model (SCM) describing detailed metabolic processes verified the predictive ability of the hybrid model (when compared with experimental data) and highlighted the practical difficulties involved in utilizing complex models. Global sensitivity analysis (GSA) on the hybrid model identified the specific transcription and translation rates of heavy and light immunoglobulin chains as parameters with the largest impact on the antibody production process. This information, together with the addition of a 24-h lag phase, resulted in the successful extension of the hybrid model to represent GS-NS0 system behavior under hyperosmotic culture conditions.
Ho
Yingswan
Y
Department of Chemical Engineering, Imperial College London, South Kensington campus, London SW7 2AZ, United Kingdom.
Varley
Julie
J
Mantalaris
Athanasios
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D003198:Computer Simulation; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D009194:Myeloma Proteins / Q000378:metabolism*; D009997:Osmotic Pressure; D015202:Protein Engineering / Q000379:methods*; D020543:Proteome / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D009194:Myeloma Proteins; D020543:Proteome; D011994:Recombinant Proteins