Application of maltose as energy source in protein-free CHO-K1 culture to improve the production of recombinant monoclonal antibody

Abstract

Oligosaccharides are generally considered to be un-utilized for growth of mammalian cells because their permeability across the cell membrane is low. However, in our previous study, we discovered that CHO and HEK293 cells consume maltose in culture media without serum and glucose. This is interesting because the transporter for maltose in mammalian cells has not been discovered to-date, and the only animal disaccharide transporter that is recently discovered is a sucrose transporter. The application of oligosaccharides in mammalian cell-based biopharmaceutical manufacturing can be beneficial, because it can theoretically increase carbohydrate content of the culture medium and decrease lactate production. Here, we first determined that specific maltose consumption rate in CHO cells was similar to galactose and fructose at 0.257 ng/cell/day. We then demonstrated that CHO cells can be cultivated with reasonable cell growth using higher maltose concentrations. After which, we evaluated the use of maltose supplementation in the production of a recombinant monoclonal antibody in batch and fed-batch cultures, demonstrating improvements in recombinant monoclonal antibody titer of 15% and 23% respectively. Finally, glycosylation profiles of the antibodies were analyzed.