Predictive macroscopic modeling of cell growth, metabolism and monoclonal antibody production: Case study of a CHO fed-batch production
| Autor: | Bassem Ben Yahia, Elmar Heinzle, Laetitia Malphettes |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
In silico Metabolite Cell Bioengineering CHO Cells 01 natural sciences Applied Microbiology and Biotechnology 03 medical and health sciences chemistry.chemical_compound Cricetulus Cricetinae 010608 biotechnology Extracellular medicine Animals 030304 developmental biology 0303 health sciences Chemistry Cell growth Chinese hamster ovary cell Antibodies Monoclonal Cell biology medicine.anatomical_structure Batch Cell Culture Techniques Cell culture Antibody Formation Intracellular Biotechnology |
| Zdroj: | Metabolic Engineering. 66:204-216 |
| ISSN: | 1096-7176 |
| DOI: | 10.1016/j.ymben.2021.04.004 |
| Popis: | We describe a systematic approach to establish predictive models of CHO cell growth, cell metabolism and monoclonal antibody (mAb) formation during biopharmaceutical production. The prediction is based on a combination of an empirical metabolic model connecting extracellular metabolic fluxes with cellular growth and product formation with mixed Monod-inhibition type kinetics that we generalized to every possible external metabolite. We describe the maximum specific growth rate as a function of the integral viable cell density (IVCD). Moreover, we also take into account the accumulation of metabolites in intracellular pools that can influence cell growth. This is possible even without identification and quantification of these metabolites as illustrated with fed-batch cultures of Chinese Hamster Ovary (CHO) cells producing a mAb. The impact of cysteine and tryptophan on cell growth and cell productivity was assessed, and the resulting macroscopic model was successfully used to predict the impact of new, untested feeding strategies on cell growth and mAb production. This model combining piecewise linear relationships between metabolic rates, growth rate and production rate together with Monod-inhibition type models for cell growth did well in predicting cell culture performance in fed-batch cultures even outside the range of experimental data used for establishing the model. It could therefore also successfully be applied for in silico prediction of optimal operating conditions. |
| Databáze: | OpenAIRE |
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