The combined effect of sodium butyrate and low culture temperature on the production, sialylation, and biological activity of an antibody produced in CHO cells

Cell cultures containing 0 similar to 5 mM sodium butyrate (NaBu) and grown at 30 and 37A degrees C were conducted to investigate the combined effect of NaBu and low temperature on the quantity and quality of an antibody production in CHO cells. Although NaBu addition decreased cell viability by apoptosis in a dose-dependent manner at both 30 and 37A degrees C, the onset of significant apoptosis induced by NaBu was delayed by lowering culture temperature. The highest specific antibody productivity (q (p)) of 23.26 pg/cell/day was obtained in the culture containing 2 mM NaBu at 30A degrees C; however, the highest antibody concentration of 167.84 mg/L was achieved in the culture containing 1 mM NaBu at 30A degrees C, as the detrimental effect of further NaBu addition on cell growth compromised its beneficial effect on q (p). Moreover, protein quality with respect to the total sialic acid content and Nglycolylneuraminic acid (Neu5Gc) level was evaluated. There were no apparent changes regarding the total sialic acid content of the antibody, but manipulation of cultures with NaBu treatment or (and) low culture temperature did decrease Neu5Gc levels by 5 similar to 10%. Biological activity of the antibody was also assessed, and no obvious changes were observed. Collectively, the simultaneous application of NaBu and low culture temperature was an effective way to extend culture period and enhance final antibody concentration, without compromising the sialic acid content or biological activity.