Increase in both productivity and product yields in biopharmaceutical process development with recombinant protein producing mammalian cells can be mainly attributed to the advancements in cell line development, media, and process optimization. Only recently, genome-scale technologies enable a system-level analysis to elucidate the complex biomolecular basis of protein production in mammalian cells promising an increased process understanding and the deduction of knowledge-based approaches for further process optimization. Here, the use of gene expression profiling for the analysis of a low titer (LT) and high titer (HT) fed batch process using the same IgG producing CHO cell line was investigated. We found that gene expression (i) significantly differed in HT versus LT process conditions due to differences in applied chemically defined, serum-free media, (ii) changed over the time course of the fed batch processes, and that (iii) both metabolic pathways and 14 biological functions such as cellular growth or cell death were affected. Furthermore, detailed analysis of metabolism in a standard process format revealed the potential use of transcriptomics for rational media design as is shown for the case of lipid metabolism where the product titer could be increased by about 20% based on a lipid modified basal medium. The results demonstrate that gene expression profiling can be an important tool for mammalian biopharmaceutical process analysis and optimization.
komplexer technischer Systeme in Magdeburg. Hauptarbeitsgebiete: Modellbildung, Simulation und Regelung von verfahrenstechnischen und bioverfahrenstechnischen Prozessen, Strukturierung integrierter Navigationssysteme. Adresse: ISR, Universität Stuttgart, Pfaffenwaldring 9, D-70550 Stuttgart. Im vorliegenden Aufsatz wird sowohl das Zellwachstum als auch die Produktbildung von Hybridomazellen zur Produktion von monoklonalen Antikörpern durch ein metabolisch strukturiertes mathematisches Modell beschrieben. Auf der Grundlage von Modellsimulationen erfolgt die Untersuchung des dynamischen Verhaltens der Zellkultur. Darüber hinaus werden modellgestützte Verfahren zur Prozeßüberwachung und Prozeß-führung entworfen und im Labormaßstab für einen Antikörperproduktionsprozeß mit einer Hybridomazellkultur eingesetzt. Die dabei erhaltenen Ergebnisse zeigen, daß eine deutliche Verbesserung der Wirtschaftlichkeit des Produktionsprozesses durch diese Verfahren erreichbar ist.
Metabolie structured modeling and model-based control of animal cell culturesThis article decribes a metabolic structured mathematical model for the growth and monoclonal antibody production behavior of hybridoma cells in culture. The dynamic behavior of the cell culture is examined by model simulation studies. Model-based methods of process monitoring and control are designed and applied to an antibody production process in lab scale. The results show that a significant improvement of the process economics can be achieved by these methods.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.