Ehancement of Antibody Productivity in the Near-Zero Specific Growth Rate During Glucose and Glutamine-Limited Fed-Batch Culture of Hybridoma Cells

Abstract

A set of fed-batch cultures feeding concentrated nutrients was carried out to find out the optimal feeding policy to give higher antibody productivity in the fed-batch culture. From the experiments, it was found that there were two different trends in the relationship between the antibody productivity and the specific growth rate. The specific antibody productivity (g/gCel/hr) was found to significantly increase (327 % over the average of other growth rates) when the apparent specific growth rate was lowered to 0.01 hr−1 This might be caused by the increased fraction of G1-arrested cells in this low specific growth rate in the fed-batch culture as proposed by Linardos et al.(1992) and Suzuki el al.(1989) in their cell cycle model. On the other hand, there was little difference in the specific antibody productivity beyond this specific growth rate. The final antibody titer was higher in the higher specific growth rates beyond 0.01 hr−1 (150% higher at 0.04 than at 0.0175 hr−1 possibly due to the higher viable cell density. Therefore, to get higher antibody productivity, it might be better to start with or grow to the higher viable cell density and then the specific growth rate should be maintained in thenear-zero (0.01 hr−1 in this study) to get highest concentration of G1-arrested cells as possible. In this paper, fed-batch data at near- zero specific growth rate are compared with data of batch culture and fed-batch culture at high growth rate.Keywordshybridomafed-batchmonoclonal antibodynear-zero growthsubstrate limitation