Enhancement of sialylation on humanized IgG-like bispecific antibody by overexpression of α2,6-sialyltransferase derived from Chinese hamster ovary cells

Appl Microbiol Biotechnol. 2012 Apr;94(1):69-80. doi: 10.1007/s00253-011-3814-1. Epub 2011 Dec 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / genetics
  • Antibodies, Bispecific / metabolism*
  • Antibodies, Monoclonal, Humanized / genetics
  • Antibodies, Monoclonal, Humanized / metabolism*
  • CHO Cells
  • Cricetinae / genetics
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • Gene Expression*
  • Humans
  • Immunoglobulin G / genetics
  • Immunoglobulin G / metabolism*
  • Ovary / enzymology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sialyltransferases / genetics*
  • Sialyltransferases / metabolism
  • Up-Regulation
  • beta-D-Galactoside alpha 2-6-Sialyltransferase

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Recombinant Proteins
  • Sialyltransferases
  • beta-D-Galactoside alpha 2-6-Sialyltransferase