EFFECT OF THE MACROMOLECULAR COMPOSITION OF MURINE HYBRIDOMA CELLS ON ANTIBODY PRODUCTIVITY IN BATCH AND FED-BATCH CULTURE
      J. D. Jang and J. P. Barford*
      Dept. of Chemical Engineering, Sydney University
      Sydney, NSW 2006 ,Australia

      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 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 macromolecular composition  and antibody production to get higher antibody productivity. In this study, we searched for an optimum feeding strategy by changing the target growth rate  in fed-batch culture  to give higher antibody productivity in terms of macromolecular composition.  To quantify  macromolecular  metabolism in animal cell, model equations for macromolecular metabolism were incorporated into the previous structured  model developed by our group, which simulates dynamic nutrient utilisation  and cell growth in the culture of hybridoma cells. Simulation results from  the updated model were compared with macromolecular profiles of experimental data.