Abstract
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.