Determination of Chinese hamster ovary cell line stability and recombinant antibody expression during long-term culture

Biotechnology and Bioengineering

Volumn 109, Issue 8, 2012, Pages 2093-2103

  Bailey, Laura A ^a,c   Hatton, Diane ^b   Field, Ray ^b   Dickson, Alan J ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b MEDIMMUNE   (United States)

^c Estuary Banks   (United Kingdom)

Author keywords

Cell stress; GADD153; Instability; Metabolism; Phenotypic drift; Post transcriptional

Indexed keywords

ANTIBODY PRODUCTION; BATCH CULTURE; CELL LINES; CELL STRESS; CELLULAR METABOLISM; CELLULAR PHENOTYPES; CELLULAR STRESS; CHINESE HAMSTER OVARY CELLS; CHO CELL; EXTRACELLULAR; GADD153; GENE COPY NUMBER; LONG-TERM CULTURE; MOLECULAR LEVELS; MRNA EXPRESSION; PHENOTYPIC DRIFT; POST-TRANSCRIPTIONAL; POST-TRANSLATIONAL MODIFICATIONS; PROCESS YIELD; PROTEIN EXPRESSIONS; RECOMBINANT ANTIBODY; THERAPEUTIC PROTEIN; TIME VALUES;

AMINO ACIDS; BATCH CELL CULTURE; CELLS; CYTOLOGY; GENE ENCODING; GLUCOSE; METABOLISM; MONOCLONAL ANTIBODIES; PLASMA STABILITY; PROTEINS; STABILITY;

GENE EXPRESSION;

ALANINE; GLUCOSE; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; IMMUNOGLOBULIN G ANTIBODY; LACTIC ACID; MESSENGER RNA; OLIGOSACCHARIDE; RECOMBINANT ANTIBODY;

ANIMAL CELL; ANIMAL CELL CULTURE; ANTIBODY PRODUCTION; ANTIBODY TITER; ARTICLE; BACTERIUM CULTURE; CELL METABOLISM; CELL STRESS; CELL VIABILITY; CHO CELL; CONTROLLED STUDY; FEMALE; GADD153 GENE; GENE; GENE DOSAGE; GENE EXPRESSION; IMMUNOGLOBULIN HEAVY CHAIN GENE; IMMUNOGLOBULIN LIGHT CHAIN GENE; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; TIME;

ANIMALS; ANTIBODIES; BIOTECHNOLOGY; CHO CELLS; CRICETINAE; CRICETULUS; GENOMIC INSTABILITY; RECOMBINANT PROTEINS;

CRICETULUS GRISEUS;

EID: 84862679986     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.24485     Document Type: Article

References (35)

1. Altamirano C, Illanes A, Becerra S, Cairó JJ, Gòdia F. 2006. Considerations on the lactate consumption by CHO cells in the presence of galactose. J Biotechnol 125: 547- 556.
2. Altamirano C, Berrios J, Vergara M. 2009. Galactose and lactate as nutrients in continuous cultures of CHO cells producing rh-tPA. New Biotechnol 25: S239- S239.
3. Arden N, Betenbaugh MJ. 2006. Regulating apoptosis in mammalian cell cultures. Cytotechnology 50: 77- 92.
4. Barnes LM, Bentley CM, Dickson AJ. 2003. Stability of protein production from recombinant mammalian cells. Biotechnol Bioeng 81: 631- 639.
5. Birch J, Bebbington CR, Field R, Renner G, Brand H, Finney H. 1993. The production of recombinant antibodies using the glutamine synthetase (GS) system, Vol. 5, Dordrecht: Kluwer Academic Publishers.
6. Bonarius HPJ, Özemre A, Timmerarends B, Skrabal P, Tramper J, Schmid G, Heinzle E. 2001. Metabolic-flux analysis of continuously cultured hybridoma cells using mass spectrometry in combination with 13C-lactate nuclear magnetic resonance spectroscopy and metabolite balancing. Biotechnol Bioeng 74: 528- 538.
7. Brown M, Renner G, Field RP, Hassell T. 1992. Process development for the production of recombinant antibodies using the glutamine synthetase (GS) system. Cytotechnology 9: 231- 236.
8. Bruhat A, Jousse C, Wang XZ, Ron D, Ferrara M, Fafournoux P. 1997. Amino acid limitation induces expression of CHOP, a CCAAT/enhancer binding protein-related gene, at both transcriptional and post-transcriptional levels. J Biol Chem 272: 17588- 17593.
9. Chusainow J, Yang Y, Yeo JHM, Toh PC, Asvadi P, Wong NSC, Yap M, G S. 2009. A study of monoclonal antibody-producing CHO cell lines: What makes a stable high producer? Biotechnol Bioeng 102: 1182- 1196.
10. Derouazi M, Martinet D, Besuchet Schmutz N, Flaction R, Wicht M, Bertschinger M, Hacker DL, Beckmann JS, Wurm FM. 2006. Genetic characterization of CHO production host DG44 and derivative recombinant cell lines. Biochem Biophys Res Commun 340: 1069- 1077.
11. Dorai H, Corisdeo S, Ellis D, Kinney C, Chomo M, Hawley-Nelson P, Moore G, Betenbaugh MJ, Ganguly S. 2011. Early prediction of instability of chinese hamster ovary cell lines expression recombinant antibodies and antibody-fusion proteins. Biotechnol Bioeng 109: 1016- 1030.
12. Erhardt P, Toth A, Fribley A, Zhang K, Kaufman RJ. 2009. Regulation of apoptosis by the unfolded protein response. In: Walker JM, editor. Apoptosis, Vol. 559, New York: Humana Press. p 191- 204.
13. Freedman DA. 2005. Statistical models: Theory and practice. Cambridge, UK: Cambridge University Press. ISBN 9780521671057.
14. Goudar C, Biener R, Boisart C, Heidemann R, Piret J, de Graaf A, Konstantinov K. 2009. Metabolic flux analysis of CHO cells in perfusion culture by metabolite balancing and 2D [13C, 1H] COSY NMR spectroscopy. Metab Eng 12: 138- 149.
15. Hacker DL, Wurm FM. 2008. Recombinant protein production yields from mammalian cells: Past, present, and future. BioPharm Int Suppl 21: 6- 15.
16. Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D. 2000. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell 6: 1099- 1108.
17. Jiang Z, Huang Y, Sharfstein ST. 2006. Regulation of recombinant monoclonal antibody production in chinese hamster ovary cells: A comparative study of gene copy number, mRNA level, and protein expression. Biotechnol Prog 22: 313- 318.
18. Kennard ML, Goosney DL, Monteith D, Zhang L, Moffat M, Fischer D, Mott J. 2009. The generation of stable, high MAb expressing CHO cell lines based on the artificial chromosome expression (ACE) technology. Biotechnol Bioeng 104: 540- 553.
19. Kim SJ, Lee GM. 1999. Cytogenetic analysis of chimeric antibody-producing CHO cells in the course of dihydrofolate reductase-mediated gene amplification and their stability in the absence of selective pressure. Biotechnol Bioeng 64: 741- 749.
20. Kim NS, Kim SJ, Lee GM. 1998. Clonal variability within dihydrofolate reductase-mediated gene amplified Chinese hamster ovary cells: Stability in the absence of selective pressure. Biotechnol Bioeng 60: 679- 688.
21. Kim R, Emi M, Tanabe K, Murakami S. 2006. Role of the unfolded protein response in cell death. Apoptosis 11: 5- 13.
22. Kim M, O'Callaghan PM, Droms KA, James DC. 2011. A mechanistic understanding of production instability in CHO cell lines expressing recombinant monoclonal antibodies. Biotechnol Bioeng 108: 2434- 2446.
23. Lengwehasatit I, Dickson AJ. 2002. Analysis of the role of GADD153 in the control of apoptosis in NS0 myeloma cells. Biotechnol Bioeng 80: 719- 730.
24. Li J, Holbrook NJ. 2004. Elevated gadd153/chop expression and enhanced c-Jun N-terminal protein kinase activation sensitizes aged cells to ER stress. Exp Gerontol 39: 735- 744.
25. Lu S, Sun X, Zhang Y. 2005. Insight into metabolism of CHO cells at low glucose concentration on the basis of the determination of intracellular metabolites. Process Biochem 40: 1917- 1921.
26. McCullough KD, Martindale JL, Klotz L-O, Aw T-Y, Holbrook NJ. 2001. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 21: 1249- 1259.
27. O'Callaghan PM, McLeod J, Pybus LP, Lovelady CS, Wilkinson SJ, Racher AJ, Porter A, James DC. 2010. Cell line-specific control of recombinant antibody production by CHO cells. Biotechnol Bioeng 106: 938- 951.
28. Osterlehner A, Silke S, Göpfert U. 2011. Promoter methylation and transgene copy numbers predict unstable protein production in recombinant chinese hamster ovary cell lines. Biotechnol Bioeng 108: 2670- 2681.
29. Oyadomari S, Mori M. 2003. Roles of CHOP//GADD153 in endoplasmic reticulum stress. Cell Death Differ 11: 381- 389.
30. Pouysségur J, Shiu RPC, Pastan I. 1977. Induction of two transformation-sensitive membrane polypeptides in normal fibroblasts by a block in glycoprotein synthesis or glucose deprivation. Cell 11: 941- 947.
31. R Development Core Team. 2011. R: A language and environment for statistical computing. R Foundation for statistical computing, Vienna, Austria. ISBN 3-900051-07-0;
32. Ron D, Habener JF. 1992. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev 6: 439- 453.
33. Ross J. 1995. mRNA stability in mammalian cells. Microbiol Rev 59: 423- 450.
34. Sellick CA, Hansen R, Maqsood AR, Dunn WB, Stephens GM, Goodacre R, Dickson AJ. 2009. Effective quenching processes for physiologically valid metabolite profiling of suspension cultured mammalian cells. Anal Chem 81: 174- 183.
35. Wurm FM. 2004. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22: 1393- 1398.