The combined effect of sodium butyrate and low culture temperature on the production,sialylation, and biological activity of an antibody produced in CHO cells |
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Authors: | Fei Chen Tianci Kou Li Fan Yan Zhou Zhaoyang Ye Liang Zhao Wen-Song Tan |
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Institution: | (1) National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, 11, Ireland; |
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Abstract: | Cell cultures containing 0 ∼ 5 mM sodium butyrate (NaBu) and grown at 30 and 37°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 37°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 30°C; however, the highest antibody concentration
of 167.84 mg/L was achieved in the culture containing 1 mM NaBu at 30°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 ∼ 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. |
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