Applied Microbiology and Biotechnology, Vol.94, No.1, 69-80, 2012
Enhancement of sialylation on humanized IgG-like bispecific antibody by overexpression of alpha 2,6-sialyltransferase derived from Chinese hamster ovary cells
Improvement of glycosylation is one of the most important topics in the industrial production of therapeutic antibodies. We have focused on terminal sialylation with alpha-2,6 linkage, which is crucial for anti-inflammatory activity. In the present study, we have successfully cloned cDNA of beta-galactosyl alpha-2,6 sialyltransferase (ST6Gal I) derived from Chinese hamster ovary (CHO) cells regardless of reports that stated this was not endogenously expressed in CHO cells. After expressing cloned ST6Gal I in Escherichia coli, the transferase activity was confirmed by HPLC and lectin binding assay. Then, we applied ST6Gal I to alpha-2,6 sialylation of the recombinant antibody; the ST6Gal I expression vector was transfected into the CHO cell line producing a bispecific antibody. The N-glycosylation pattern of the antibody was estimated by HPLC and sialidase digestion. About 70% of the total N-linked oligosaccharide was alpha-2,6 sialylated in the transfected cell line whereas no sialylation was observed in the non-transfected cell line. The improvement of sialylation would be of practical importance for the industrial production of therapeutic antibodies.
Keywords:Chinese hamster ovary (CHO) cell;Antibody production;Glycosylation control;Sialylation;Beta-galactosyl alpha-2,6 sialyltransferase (ST6Gal I);Bispecific diabody