Screening and development of natural compounds as tools to improve IgG production and quality in recombinant CHO cell culture

The clonal producer cell lines are inherently variable and hardly predictable, despite the various advances in the field of biopharmaceutical production. These features are inherent to the process and are difficult to control. The number of strategies available to salvage a batch culture with undesired behaviour is limited, and this causes uncertainty in the production process. During the present study, chemicals which had favourable traits and were previously described in unrelated fields of literature, were selected and screened, in order to identify possible improvements in the final and specific productivity. Of those selected, catechins and resveratrol were further investigated in order to check their effect on the cell cycle, to optimize their addition in scale-up cultures and to check their effect on the quality of the monoclonal antibody. Resveratrol and the compounds from the catechin group, were able to increase the specific productivity by approximately 2.5 and 2-fold respectively. This was achieved by cytostaticity. Studies of resveratrol and catechins on cell cycle, showed that these chemicals stopped the cell cycle in the S and G2/M phase. This was probably due to their effect on topoisomerases. Furthermore, when added at late stages of the culture during the optimization experiments, resveratrol and catechin improved the final titre by 1.37- and 1.43-fold increase respectively, without causing any negative effects. Finally, the quality assessment of the monoclonal antibody did not show any changes in aggregation or fragmentation. Resveratrol and catechin caused a decrease of the acidic species by 6.75 ± 3.91% and 3.58 ± 0.28 respectively. The mass spectrometry analysis showed that the treated samples were less likely to suffer reduction in the variable region, indicating that these chemicals could preserve the antigen recognition site. The present study suggests that resveratrol and catechin are promising additives that could improve the recombinant monoclonal antibody production and preserve the product from undesired degradation and modifications with potential improvements of the shelf-life and potency