Specific monoclonal antibody productivity and the cell cycle-comparisons of batch,continuous and perfusion cultures |
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Authors: | Mohamed Al-Rubeai A N Emery S Chalder D C Jan |
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Institution: | (1) Centre for Biochemical Engineering, School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT Birmingham, UK |
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Abstract: | A selection of mouse hybridoma cell lines showed a variation of approximately two orders of magnitude in intracellular monoclonal
antibody contents. The different levels directly influenced apparent specific monoclonal antibody productivity during the
death phase but not during the growth phase of a batch culture. The pattern of changes in specific productivity during culture
remained basically similar even though at different levels for all cell lines tested. Arresting the cells in the G1 phase using thymidine increased the specific productivity, cell volume and intracellular antibody content but at the same
time led to decreased viability. In continuous culture DNA synthesis decreased with decreasing dilution rate though without
an accompanying change in cell cycle and cell size distributions. The data shows both the decrease in viability and intracellular
antibody content to be important factors which influence the negative association between specific antibody productivity and
growth rate. In high cell density perfusion culture, when the cell cycle was prolonged by slow growth, viability was low and
dead, but not lysed, cells were retained in the system, the specific antibody productivity was nearly two fold higher than
that obtained in either batch or continuous cultures. The results imply that the prolongation of G1 phase and the increase in death rate of cells storing a large amount of antibody together cause an apparent increase in specific
antibody productivity. |
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Keywords: | monoclonal antibody hybridoma cell cycle flow cytometry |
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