Increasing viable cell densities has been a means to increase the associated volumetric productivity of cell cultures. However, uncontrolled proliferation of cells is undesirable due to operational challenges within large-scale bioreactors. Previous methods to arrest growth and control cell mass include temperature shifts; addition of chemical additives (such as DMSO or sodium butyrate); nutrient limitation; or cell line engineering strategies. In this study, we demonstrate the use of cell cycle inhibitors in multiple recombinant mAb producing CHO cell lines to achieve growth arrest and increasing specific productivity by 2-3 fold. Although a similar increase in specific productivity can be achieved using thermally induced growth arrest, a shift in the production of mAbs expressing non-desirable high mannose glycans was also evident. mAbs produced in the presence of the small molecule cell cycle inhibitor resulted in further processing of glycans with a decrease in high mannose species offset with an increase in galactosylated species. The difference in glycosylation during temperature shifts was attributed to decreased mRNA levels of multiple regulatory genes of the N-linked glycosylation pathway which was not evident in the presence of these small molecule inhibitors. In closing, the use of these small molecule cell cycle inhibitors can be used to optimize cell culture processes resulting in optimal cell growth, specific productivity, and glycosylation profiles of the target recombinant antibody.<br/>

Achieving cell growth control and increased specific productivity in CHO cell cultures without impacting product quality

251st National Meeting (2016)

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