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

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)
Publication Information
Microbiology and Biotechnology Letters / v.34, no.1, 2006 , pp. 47-51 More about this Journal
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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1 Castro, P. M. L., P. M. Hayter, A. P. Ison, and A. T. Bull. 1992. Application of a statical design to the optimization of culture medium for recombinant interferon-gamma production by chinese hamster ovary cells. Appl. Microbial. Biotechnol. 38: 84-90
2 Gebert, C. A., and P. P. Gray. 1995. Expression of FSH in CHO cells. Stimulation of hFSH expression levels by defined medium supplements. Cytotechnology 17: 13-19   DOI   ScienceOn
3 Hunt, S. M., S. C. Pak, M. W. Bridges, P. P. Gray, and M. J. Sleighi. 1997. Chinese hamster ovary cells produce sufficient recombinant insulin-like growth factor I to support growth in serum-free medium. Cytotechnology 24: 55-64   DOI   ScienceOn
4 Kim, N. S., and G. M. Lee. 2001. Overexpression of bcl-2 inhibits sodium butyrate-induced apotosis in chinese hamster ovary cells, resulting in enhanced humanized antibody production. Biotechnol. Bioeng. 71: 184-193   DOI   ScienceOn
5 Lee, M. S., and G. M. Lee. 2000. Hyperosmotic pressure enhances immunoglobulin transcription rates and secretion rates of KR12H-2 transfectoma. Biotechnol. Bioeng. 68: 260-268   DOI   ScienceOn
6 Leeders, W, H. Glansbeek, W. De Bruin., and S. Yap. 1990. Binding of the major and large HBsAg to human hepatocytes and liver plasma membrane: Putative external and internal receptors for infection and secretion of hepatitis B virus. Hepatology 12: 141-147   DOI
7 Mastrangelo, A. J., and M. J. Betenbaugh. 1998. Overcoming apoptosis: new methods for improving protein-expression systems. TIBTECH 16: 88-95   DOI
8 Oster, T., C. Thioudellt, J. Chevalot, C. Masson, M. Wellman, A. Marc, and G. Siest. 1993. Induction of recombinant human y-glutamyl transferase by sodium butyrate in transfected V79 and CHO Chinese hamster cells. Biochem. Biophys. Res. Commun. 193: 406-412   DOI   ScienceOn
9 Moore, A., J. Mercer, J. Dutina, C. J. Donahue., K. D. Bauer, J. P. Mather, T. Etcheverry, and T. Ryll. 1997. Effects of temperature shifts on cell cycle, apotosis and nucleotide pools in CHO cell batch cultures. Cytotechnology 23: 47-54   DOI   ScienceOn
10 Keen, M. J. and M. T. Rapson. 1995. Development of a serum-free culture medium or the large scale production of recombinant protein from a chinese hamster ovary cell line. Cytotechnology 17: 153-163   DOI   ScienceOn
11 Yook, S. K., Y. Ahn, and K. Han. 2001. Enhancement of recombinant erythropoietin production in CHO cells in an incubator without $CO_2$ addition. Cytotechnology 37: 119-132   DOI   ScienceOn
12 Blumberg, B. S. 1977. Australian antigen and the biology of Hepatitis B. Science. 41: 293-311   DOI
13 Hertogs, K., W. Leenders, E. Depla, W. De Bruin, L. Meheus, J. Raymackers, H. Moshage, and S. Yap. 1993. Endotoxin II, present on human liver plasma membrane, is a specific hepatitis B virus (HBY) envelope protein. Virology 197: 549-557   DOI   ScienceOn
14 Kim, T. K., J. S. Ryu, J. Y. Chung, M. S., and G. M. Lee. 2000. Osmoprotective effect of glycine betaine on thrombopoietin production in hyperosmotic chinese hamster ovary cell culture: Clonal variations. Biotechnol. Prog. 16: 775-781   DOI   ScienceOn
15 Kim, N. S., K. H. Chang, B. S. Chung, S. H. Kim, J. H. Kim, and G. M. Lee. 2003. Characterization of humanized antibody produced by apoptosis-resistant CHO cells under sodium butyrate-induced condition. J. Microbiol. Biotechnol. 13: 926-936
16 Chisari, F. V, C. Ferrari. 1995. Hepatitis B virus immunopathogenesis. Anual Rev. lmmunol. 13: 29-62
17 Kim, N. S., and G. M. Lee. 2002. Inhibition of sodium butyrate-induced apoptosis in recombinant Chinese hamster ovary cells by constitutively expressing antisense RNA of Caspase-3. Biotechnol. Bioeng. 78: 217-228   DOI   ScienceOn
18 Ryu, J. S., T. K. Kim, J. Y. Chung, and G. M. Lee. 2000. Osmoprotective effect of glycine betaine on foreign protein in hyperosmotic recombinant chinese hamster ovary cell cultures differs among cell line. Biotechnol. Bioeng. 70: 167-175   DOI   ScienceOn
19 Medhi, H., M. Kaplan, F. Anlar, X. Yang, R. Bayer, K. Sutherland, and M. Peeples. 1994. Hepatitis B virus surface antigen binds to apolipoprotein H. J. Viral. 68: 2415-2424
20 Oh, H. K., M. K. So, J. H. Yang, H. C. Yoon, J. S. Ahn, J. M. Lee, J. T. Kim, J. U, Yoo, and T. H. Byun. 2005. Effect of N-Acetylcystein on butyrate-treated chinese hamster ovary cells to improve the production of recombinant human interferon${\beta}$-la. Biotechnol. Prag. 21: 1154-1164   DOI   ScienceOn
21 Cherlet, M., A. Marc. 2000. Stimulation of monoclonal antibody production of hybridoma cells butyrate: evaluation of a feeding strategy and characterization of cell behaviour. Cytotechnology 32: 17-29   DOI   ScienceOn
22 Oh, S. K. W., P. Vig., F. Chua, W. K. Teo, and M. G. S. Yap. 1993. Substantial overproduction of antibodies by applying osmotic pressure and sodium butyrate. Biotechnol. Bioeng. 42: 601-610   DOI   ScienceOn
23 Arts, J., M. Lansink, J. Grimbergen, K. H. Toet, and T. Kooistar. 1995. Stimulation of tissue-type plasminogen activator gene expression by sodium butyrate and trichostatin A in human endothelial cells involves histone acetylation. Biochem. J. 310: 171-176   DOI