文献类型：期刊文献

中文题名：基于细胞周期调控的 CHO 细胞强化流加补料工艺提高重组抗体表达效率

英文题名：Development of an intensified fed-batch process to enhance recombinant antibody productivity of CHO cells based on cell cycle regulation

作者：Xiao, Shang[1]; Yin, Pei[1]; Zhou, Junqi[2]; Li, Weifeng[1]; Molish, Ali[1]; Guo, Meijin[1]

机构：[1] State Key laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; [2] Shanghai TopAlliance Biosciences Co., Ltd., Shanghai, 201318, China

年份：2026

卷号：42

期号：5

起止页码：2209

外文期刊名：Shengwu Gongcheng Xuebao/Chinese Journal of Biotechnology

收录：EI(收录号：20262620974669)

语种：中文

外文关键词：Batch data processing - Cell culture - Cell growth - Cell proliferation - Plants (botany)

摘要：Chinese hamster ovary (CHO) cells are the most widely used hosts for biopharmaceutical production, yet their low recombinant antibody expression efficiency remains one of key bottlenecks in industrial applications. To enhance anti-EGFRv III antibody expression in CHO cells, an intensified fed-batch process was successfully developed for Cell A and Cell B cell strains based on cell cycle regulation. First, flow cytometry was used to establish the relationship between cell cycle distribution and specific antibody production rate (Qp). The results showed that the proportions of cells in the G0/G1 phase increased significantly over time, reaching 50% and 64% on day 12 for Cell A and Cell B, respectively. Meanwhile, the single-cell Qp increased by 1.5 folds (Cell A) and 1.0 fold (Cell B) compared with initial levels. Higher proportions of cells in the G0 and G1 phases could significantly boost Qp, however, impair cell growth and accumulation, leading to a reduction in total antibody titer. To address this, we implemented feeding during the N-1 seed stage and extended the culture time. At harvest, the densities of Cell A and Cell B reached 26.3×106 cells/mL and 17.7×106 cells/mL, with the proportions of cells in G0/G1 phase increasing to 45% and 38%, respectively. After inoculation of high-density seed cultures into 5 L bioreactors and continuing culture for 14 days, the integrated viable cell density (IVCD) of both Cell A and Cell B exceeded that of the conventional process. In addition, the treatment increased the Qp by 11.0% and 9.1% and achieved final antibody titers of 9.5 g/L and 5.0 g/L for Cell A and Cell B, respectively, with no significant impact on critical quality attributes of recombinant antibody. In summary, the intensified fed?batch process established in this study for CHO cells, based on cell cycle regulation, simultaneously enhances cell accumulation and specific productivity, ultimately significantly improving the recombinant antibody expression levels in CHO cells. Therefore, this intensified fed-batch process can be adopted for recombinant antibody production by CHO cells cultivated at an industrial scale. ?2026 Chin J Biotech, All rights reserved.