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添加牛磺酸的细胞培养基可降低单克隆抗体的碱性电荷变体水平。

Cell culture medium supplemented with taurine decreases basic charge variant levels of a monoclonal antibody.

作者信息

Liu Mengjuan, Wang Jiaqi, Tang Hongping, Fan Li, Zhao Liang, Wang Hai-Bin, Zhou Yan, Tan Wen-Song

机构信息

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Shanghai Bioengine Biotechnology Co. Ltd, Shanghai, 200237, China.

出版信息

Biotechnol Lett. 2018 Dec;40(11-12):1487-1493. doi: 10.1007/s10529-018-2606-4. Epub 2018 Sep 18.

Abstract

OBJECTIVE

To explore the impact of taurine on monoclonal antibody (mAb) basic charge variants in Chinese hamster ovary (CHO) cell culture.

RESULTS

In fed-batch culture, adding taurine in the feed medium slightly increased the maximum viable cell density and mAb titers in CHO cells. What's more, taurine significantly decreased the lysine variant and oxidized variant levels, which further decreased basic variant contents from 32 to 27%. The lysine variant content in the taurine culture was approximately 4% lower than that in control condition, which was the main reason for the decrease in basic variants. Real-time PCR and cell-free assay revealed that taurine played a critical role in the upregulation of relative basic carboxypeptidase and stimulating extracellular basic carboxypeptidase activities.

CONCLUSION

Taurine exhibits noticeable impact on lower basic charge variants, which are mainly due to the decrease of lysine variant and oxidized protein variants.

摘要

目的

探讨牛磺酸对中国仓鼠卵巢(CHO)细胞培养中单克隆抗体(mAb)碱性电荷变体的影响。

结果

在补料分批培养中,在补料培养基中添加牛磺酸可略微提高CHO细胞的最大活细胞密度和mAb滴度。此外,牛磺酸显著降低了赖氨酸变体和氧化变体水平,进而使碱性变体含量从32%降至27%。牛磺酸培养条件下的赖氨酸变体含量比对照条件下低约4%,这是碱性变体减少的主要原因。实时PCR和无细胞分析表明,牛磺酸在相对碱性羧肽酶的上调和刺激细胞外碱性羧肽酶活性方面起关键作用。

结论

牛磺酸对较低的碱性电荷变体有显著影响,这主要是由于赖氨酸变体和氧化蛋白变体的减少。

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