Production of Humanised Anti-hepatitis B Antibody in Butyrate-Treated Chinese Hamster Ovary Cells

Butyrate처리된 차이니즈 햄스터 난소세포에서 Hepatitis B 바이러스 인간화항체의 생산

  • Park Se-Cheol (Biotech Laboratory, Yuhan Research Institute, Yuhan Corporation) ;
  • Lee Jae-Sun (Biotech Laboratory, Yuhan Research Institute, Yuhan Corporation) ;
  • Lee Byung-Kyu (Biotech Laboratory, Yuhan Research Institute, Yuhan Corporation) ;
  • Kang Heui-Il (Biotech Laboratory, Yuhan Research Institute, Yuhan Corporation)
  • 박세철 ((주)유한양행 중앙연구소 바이오텍연구실) ;
  • 이재선 ((주)유한양행 중앙연구소 바이오텍연구실) ;
  • 이병규 ((주)유한양행 중앙연구소 바이오텍연구실) ;
  • 강희일 ((주)유한양행 중앙연구소 바이오텍연구실)
  • Published : 2006.03.01

Abstract

Sodium butyrate (NaBu) is used as an enhancer for the production of recombinant proteins in Chinese hamster ovary (CHO) cells. However, NaBu is well-known for its cytotoxic effect, thereby inducing apoptosis. CHO cells which had been engineered to express a humanised anti-HBV antibody were cultured using serum-free medium, Ex-cell 301. From a seeding density of $2{\times}10^5$ cells/ml, CHO cells grown with serum-free medium reached a maximum cell density of $1.3{\times}10^6$ cells/ml after 9 days in culture and produced a maximal antibody concentration of 130 mg/l after 13 days in culture. In the perfusion culture system, CHO cells producing anti-HBV antibody grown in an 7.5 1 bioreactor seeded with $2{\times}10^5$ cells/ml reached a maximal antibody concentration of 85 mg/1 after 720 h in culture. The addition of 0.3 mM NaBu and lowering culture temperature to $33^{\circ}C$ elongated the culture period to 60 days and increased the production yield by 2-fold, compared to control culture.

Keywords

Anti-hepatitis B antibody;Chinese hamster ovary cell;sodium butyrate (NaBu);serum-free;low temperature culture

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