Effect of the Macromolecular Metabolism of Murine Hybridoma Cells on Antibody Productivity in Batch and Fed-Batch Culture

Abstract

Batch and fed-batch cultures of a murine hybridoma cell line (AFP-27) have been performed in a stirred tank reactor to estimate effect of macromolecular composition on antibody production. Macromolecular composition was found to change dynamically during batch culture of hybridoma cells possibly due to active production of RNA and protein and high metabolic rate of total cellular carbohydrates during exponential phase. Antibody synthesis from the amino acid pool is expected to compete with production of cellular proteins. Therefore, it is necessary to examine the relationship between cell growth in terms of cellular macromolecules and antibody production. A set of fed-batch cultures of a murine hybridoma cell line (AFP-27) have been performed in a stirred tank reactor to elucidate this relationship. In this study, we searched for an optimum feeding strategy by changing the target specific growth rate in fed-batch culture to give higher antibody productivity while examining the macromolecular composition. From this study, the specific production rate of cellular protein and RNA were found to have maximum rates in the fed-batch culture with a target specific growth rate of 0.035 hr1 and to decrease with target specific growth rate below 0.035 hr1 Specific antibody production rate was found to be significantly increased in the fed-batch cultures with target specific growth rate of 0.01 hr1 in which production of cellular RNA and protein were strictly limited by slow feeding of glucose and other nutrients.KeywordsStir Tank ReactorSpecific Production RateViable Cell ConcentrationMacromolecular CompositionMaximal Viable CellThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.