EGCG improves recombinant protein productivity in Chinese hamster ovary cell cultures via cell proliferation control
Chinese hamster ovary cell lines are good manufacturing practice-certified host cells and are widely used in the field of biotechnology to produce therapeutic antibodies. Recombinant protein productivity in cells is strongly associated with cell growth. To control cell proliferation, many approaches have previously been tested including: genetic engineering, chemical additives such as cell cycle inhibitors, and temperature shift of the culture. To be widely adopted in the biopharmaceutical industry, the culture methods should be simple, uniform and safe. To this end, we examined the use a natural compound to improve the production capacity. In this study, we focused on the antioxidants, catechin polyphenols, which are found in green tea, for cell proliferation control strategies. (–)-Epigallocatechin-3-gallate (EGCG), the major catechin that induces G0/G1 cell cycle arrest, was investigated for its effect on recombinant protein production. Adding EGCG to the cell culture media resulted in slower cellular growth and longer cell longevity, which improved the specific productivity and total yield of recombinant IgG1 in batch cultures by almost 50% for an extra 2 or 3 days of culture. A lower l-glutamine consumption rate was observed in cells cultured in EGCG-containing media, which may be suggesting that there was less stress in the culture environment. Additionally, EGCG did not affect the N-glycan quality of IgG1. Our results indicated that adding EGCG only on the first day of the culture enhanced the specific productivity and total amount of recombinant protein production in batch cultures. This approach may prove to be useful for biopharmaceutical production.
KeywordsChinese hamster ovary cells (–)-Epigallocatechin-3-gallate Natural compound G0/G1 phase arrest Cell longevity Recombinant protein production
We thank Dr. Masayoshi Onitsuka for providing the IgG1-expressing CHO-K1 cell line (Onitsuka and Omasa 2015). We also thank Mrs. Hitomi Ueda and Mrs. Hiroe Amou for excellent technical assistance. This research was partially supported by the project “developing key technologies for discovering and manufacturing pharmaceuticals used for next-generation treatments and diagnoses” both from the Ministry of Economy, Trade and Industry, Japan (METI) and from Japan Agency for Medical Research and Development (AMED), Grant Number 17ae0101003h005. This work was also supported by JSPS KAKENHI Grants (JP26630433, JP26249125 and JP17H06157). We thank Michal Bell, PhD, from Edanz Group for editing the English text of a draft of this manuscript.
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Conflict of interest
The authors declare that they have no conflict of interest.
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