Screening Naturally Occurring Phenolic Antioxidants for Their Suitability as Additives to CHO Cell Culture Media Used to Produce Monoclonal Antibodies

Abstract

This study identified several antioxidants that could be used in Chinese hamster ovary (CHO)cell culture media and benefit monoclonal antibody production. The flavan-3-ols, catechin, epicatechin, epigallocatechin gallate and gallocatechin gallate all had no detrimental effect on cell viability at the concentrations tested, and they reduced the final viable cell count with a resulting rise in the cell specific productivity. The flavone, luteolin behave similarly to the flavan-3-ols. Resveratrol at 50 μM concentration resulted in the most pronounced reduction in viable cell density with minimal decrease in IgG synthesis and the largest increase in cell specific productivity. Low concentrations of α-tocopherol (35 μM) reduced viable cell density and raised cell specific productivity, but at higher concentration it had little additional effect. As high concentrations of α-tocopherol are not toxic to CHO cells, its addition as an anti-oxidant has great potential. Kaempferol up to 50 μM, curcumin up to 20 μM and piceid up to 100 μM showed little effect on growth or IgG synthesis and could be useful as antioxidants. Caffeic acid phenethyl ester was toxic to CHO cell and of no interest. Seven of the phenolic compounds tested are potential cell cycle inhibitors as well as having intrinsic antioxidant properties.

Keywords

• flavan-3-ol
• catechin
• epicatechin
• epigallocatechin gallate (EGCG)
• resveratrol
• curcumin
• monoclonal antibodies (mAb)
• immunoglobulin G (IgG)
• immunoglobulin
• chemical chaperone