Change in metabolic pathways in hybridoma growth and monoclonal antibody production

Abstract

The growth and monoclonal antibody production kinetics of a murine hybridoma cell line, A3, were investigated under the exponential growth condition in batch culture. The growth yields for both glucose and glutamine increased in the middle of their exponential growth phase. The lactate yield from glucose was reduced at the late stage of culture, while the specific oxygen uptake rate was unchanged during the exponential growth, suggesting that more glucose flux enters the tricarboxylic acid cycle [TCA cycle] to synthesize ATP during catabolism at the late stage of the exponential growth phase than at the early stage. The monoclonal antibody (MAb) yields for both glucose and glutamine were also enhanced by around twofold, whereas the specific MAb production rate was reduced by 27% at the late stage of the culture. We calculated the specific ATP synthesizing rate, q ATP, and found that it is reduced by 24% at the late stage of culture. We also found that the cell size and the protein content in a cell were reduced by 7%, equivalent to 21% of the cell volume change, and by 13%, respectively. These changes in reduction rates and the specific MAb production rates approximately agree with those in the ATP synthesizing rate during the exponential growth.