pH对重组CHO细胞生长、单抗表达及质量的影响

doi:10.13560/j.cnki.biotech.bull.1985.2015.12.037

生物技术通报 ›› 2015, Vol. 31 ›› Issue (12): 256-261.doi: 10.13560/j.cnki.biotech.bull.1985.2015.12.037

pH对重组CHO细胞生长、单抗表达及质量的影响

肖尚,邓崇飞,柯军,鄢成伟,孙文正,杨彬

广东东阳光药业有限公司，东莞 523000

收稿日期:2015-03-10 出版日期:2015-12-19 发布日期:2015-12-19
作者简介:肖尚，男，硕士研究生，研究方向:动物细胞大规模培养；E-mail:xiaoshang@hecpharm.com
基金资助:
广东省引进创新科研团队计划(201101Y0104990178)

The Effects of pH on Cell Growth, Monoclonal Antibody Expression and Quality of a Recombinant CHO Strain

Xiao Shang, Deng Chongfei, Ke Jun, Yan Chengwei, Sun Wenzheng, Yang Bin

Sunshine Lake Pharma Co.，Ltd，Dongguan 523000

Received:2015-03-10 Published:2015-12-19 Online:2015-12-19

摘要/Abstract

摘要： 在1 L反应器中探究pH对CHO细胞生长、单抗表达及质量的影响。在1 L反应器中对pH进行探究，实验研究表明当pH为7.05时最适合CHO细胞生长和抗体表达，在此条件下培养时第9天获得最高细胞密度1.54×10⁷cells/mL，在第11天获得最高抗体浓度1 355.71 mg/L。pH对pCO₂、乳酸积累、抗体的单体含量、电荷异质性和糖基化也有较大影响，当pH在6.95至7.25之间时，高pH培养能够降低乳酸积累和pCO₂，但是会导致抗体的碱性峰增加。pH两项培养能够降低细胞活力，从而提高抗体表达量。

关键词: pH, CHO细胞, 抗体, pCO₂, 电荷异质性

Abstract: It was to study the effect of pH on the growth, monoclonal antibody expression and produce quality of a rewmbinant CHO strain. The results showed that the optimal pH for cell growth and the production of monoclonal antibody(mAb)was 7.05. Under this pH, a peak viable cell density was 1.54×10⁷cells/mL at day 9 and the highest harvested antibody concentration was 1 355.71 mg/L after cultivating for 11 days. In addition, pH significantly affected the accumulation of pCO₂ and lactate in cell cultures, as well as the expressed product's quality including its monomer ratio, charge variant species, and glycosylation pattern. While pH ranging from 6.95 to 7.25, cell cultures at higher pH reduced pCO₂ and the accumulation of lactate, but led the alkaline peak of antibody increase. Cultures at 2 sets of pH decreased the cell activity, therefore increased the expression of antibody.

Key words: pH, CHO cell, antibody, pCO₂, charge variants

肖尚,邓崇飞,柯军,鄢成伟,孙文正,杨彬. pH对重组CHO细胞生长、单抗表达及质量的影响[J]. 生物技术通报, 2015, 31(12): 256-261.

Xiao Shang, Deng Chongfei, Ke Jun, Yan Chengwei, Sun Wenzheng, Yang Bin. The Effects of pH on Cell Growth, Monoclonal Antibody Expression and Quality of a Recombinant CHO Strain[J]. Biotechnology Bulletin, 2015, 31(12): 256-261.

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pH对重组CHO细胞生长、单抗表达及质量的影响

The Effects of pH on Cell Growth, Monoclonal Antibody Expression and Quality of a Recombinant CHO Strain

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