Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation

Journal of Biotechnology

Volumn 188, Issue , 2014, Pages 88-96

  Ivarsson, Marija ^a   Villiger, Thomas K ^a   Morbidelli, Massimo ^a   Soos, Miroslav ^a  

^a ETH ZURICH   (Switzerland)

Author keywords

Fucosylation; Galactosylation; Glycosylation; Hybridoma cell culture; Sialylation

Indexed keywords

CELL CULTURE PROCESS; FUCOSYLATION; GALACTOSYLATION; HYBRIDOMA CELLS; N-GLYCOSYLATION; SIALYLATION;

GLYCOSYLATION;

DISSOLVED OXYGEN; GLYCAN; IMMUNOGLOBULIN G1 ANTIBODY; MONOCLONAL ANTIBODY; POLYSACCHARIDE;

ANIMAL CELL; ARTICLE; BIOPROCESS; CELL CULTURE; CELL HETEROGENEITY; CHEMICAL STRESS; DRUG PURIFICATION; FUCOSYLATION; GLYCOSYLATION; MECHANICAL STRESS; NONHUMAN; OSMOLARITY; OXYGEN SATURATION; OXYGEN TENSION; PH; SIALYLATION; SPARGING; ANIMAL; CELL LINE; METABOLISM; MOUSE;

ANIMALS; ANTIBODIES, MONOCLONAL; CELL LINE; GLYCOSYLATION; MICE; POLYSACCHARIDES;

EID: 84908062862     PISSN: 01681656     EISSN: 18734863     Source Type: Journal    
DOI: 10.1016/j.jbiotec.2014.08.026     Document Type: Article

References (69)

1. Andersen D.C., Goochee C.F. The effect of ammonia on the O-linked glycosylation of granulocyte colony-stimulating factor produced by Chinese hamster ovary cells. Biotechnol. Bioeng. 1995, 47:96-105.
2. Baker K.N., Rendall M.H., Hills a.E., Hoare M., Freedman R.B., James D.C. Metabolic control of recombinant protein N-glycan processing in NS0 and CHO cells. Biotechnol. Bioeng. 2001, 73:188-202.
3. Bibila T.A., Robinson D.K. In pursuit of the optimal fed-batch process for monoclonal antibody production. Biotechnol. Progr. 1995, 11:1-13.
4. Bonarius H.P., Houtman J.H., Schmid G., De Gooijer C.D., Tramper J. Metabolic-flux analysis of hybridoma cells under oxidative and reductive stress using mass balances. Cytotechnology 2000, 32:97-107.
5. Borys M.C., Linzer D.I., Papoutsakis E.T. Ammonia affects the glycosylation patterns of recombinant mouse placental lactogen-I by chinese hamster ovary cells in a pH-dependent manner. Biotechnol. Bioeng. 1994, 43:505-514.
6. Borys Michael C., Dalal N.G., Abu-Absi N.R., Khattak S.F., Jing Y., Xing Z., Li Z.J. Effects of culture conditions on N-glycolylneuraminic acid (Neu5Gc) content of a recombinant fusion protein produced in CHO cells. Biotechnol. Bioeng. 2010, 105:1048-1057.
7. Boyd P.N., Lines A.C., Patel A.K. The effect of the removal of sialic acid, galactose and total carbohydrate on the functional activity of Campath-1H. Mol. Immunol. 1995, 32:1311-1318.
8. Butler M. Optimisation of the cellular metabolism of glycosylation for recombinant proteins produced by Mammalian cell systems. Cytotechnology 2006, 50:57-76.
9. Ceroni A., Maass K., Geyer H., Geyer R., Dell A., Haslam S.M. GlycoWorkbench: a tool for the computer-assisted annotation of mass spectra of glycans. J. Proteome Res. 2008, 7:1650-1659.
10. Chotigeat W., Watanapokasin Y., Mahler S., Gray P.P. Role of environmental conditions on the expression levels, glycoform pattern and levels of sialyltransferase for hFSH produced by recombinant CHO cells. Cytotechnology 1994, 15:217-221.
11. Crowell C.K., Grampp G.E., Rogers G.N., Miller J., Scheinman R.I. Amino acid and manganese supplementation modulates the glycosylation state of erythropoietin in a CHO culture system. Biotechnol. Bioeng. 2007, 96:538-549.
12. Ferrara C., Grau S., Jäger C., Sondermann P., Brünker P., Waldhauer I., Hennig M., Ruf A., Rufer A.C., Stihle M., Umaña P., Benz J. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:12669-12674.
13. Gawlitzek M., Ryll T., Lofgren J., Sliwkowski M.B. Ammonium alters N-glycan structures of recombinant TNFR-IgG: degradative versus biosynthetic mechanisms. Biotechnol. Bioeng. 2000, 68:637-646.
14. Glacken M. Development of Mathematical Descriptions of Mammalian Cell Culture Kinetics for the Optimization of Fed-Batch Bioreactors 1987, Massachusetts Institute of Technology, Cambridge, MA.
15. Goudar C.T., Joeris K., Konstantinov K.B., Piret J.M. Logistic equations effectively model mammalian cell batch and fed-batch kinetics by logically constraining the fit. Biotechnol. Progr. 2005, 21:1109-1118.
16. Grainger R.K., James David C. CHO cell line specific prediction and control of recombinant monoclonal antibody N-glycosylation. Biotechnol. Bioeng. 2013, 110:2970-2983.
17. Gramer M.J., Goochee C.F. Glycosidase activities in Chinese hamster ovary cell lysate and cell culture supernatant. Biotechnol. Progr. 1993, 9:366-373.
18. Gramer Michael J., Eckblad J.J., Donahue R., Brown J., Shultz C., Vickerman K., Priem P., Van den Bremer E.T.J., Gerritsen J., Van Berkel P.H.C. Modulation of antibody galactosylation through feeding of uridine, manganese chloride, and galactose. Biotechnol. Bioeng. 2011, 108:1591-1602.
19. Gu X., Harmon B.J., Wang D.I. Site- and branch-specific sialylation of recombinant human interferon-gamma in Chinese hamster ovary cell culture. Biotechnol. Bioeng. 1997, 55:390-398.
20. Hayter P.M., Curling E.M., Gould M.L., Baines a.J., Jenkins N., Salmon I., Strange P.G., Bull a.T. The effect of the dilution rate on CHO cell physiology and recombinant interferon-gamma production in glucose-limited chemostat culture. Biotechnol. Bioeng. 1993, 42:1077-1085.
21. Hodoniczky J., Zheng Y.Z., James David C. Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro. Biotechnol. Progr. 2005, 21:1644-1652.
22. Hooker A.D., Goldman M.H., Markham N.H., James David C., Ison A.P., Bull A.T., Strange Philip G., Salmon Ian Baines A.J., Jenkins N. N-glycans of recombinant human interferon-gamma change during batch culture of Chinese hamster ovary cells. Biotechnol. Bioeng. 1995, 48:639-648.
23. Hossler P., Khattak S.F., Li Z.J. Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology 2009, 19:936-949.
24. Hossler P., Mulukutla B.C., Hu W.-S. Systems analysis of N-glycan processing in mammalian cells. PLoS One 2007, 2:e713.
25. Jefferis R. Isotype and glycoform selection for antibody therapeutics. Arch. Biochem. Biophys. 2012, 526:159-166.
26. Jimenez Del Val I., Nagy J.M., Kontoravdi C. A dynamic mathematical model for monoclonal antibody N-linked glycosylation and nucleotide sugar donor transport within a maturing Golgi apparatus. Biotechnol. Progr. 2011, 27:1730-1743.
27. Kanda Y., Yamada T., Mori K., Okazaki A., Inoue M., Kitajima-Miyama K., Kuni-Kamochi R., Nakano R., Yano K., Kakita S., Shitara K., Satoh M. Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose, hybrid, and complex types. Glycobiology 2007, 17:104-118.
28. Kaneko Y., Nimmerjahn F., Ravetch J.V. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science (New York, N.Y.) 2006, 313:670-673.
29. Karra S., Sager B., Karim M.N. Multi-scale modeling of heterogeneities in mammalian cell culture processes. Ind. Eng. Chem. Res. 2010, 49:7990-8006.
30. Kunkel J.P., Jan D.C., Butler M., Jamieson J.C. Comparisons of the glycosylation of a monoclonal antibody produced under nominally identical cell culture conditions in two different bioreactors. Biotechnol. Progr. 2000, 16:462-470.
31. Kunkel J.P., Jan D.C., Jamieson J.C., Butler M. Dissolved oxygen concentration in serum-free continuous culture affects N-linked glycosylation of a monoclonal antibody. J. Biotechnol. 1998, 62:55-71.
32. Lakhotia S., Bauer K.D., Papoutsakis Eleftherios T. Damaging agitation intensities increase DNA synthesis rate and alter cell-cycle phase distributions of CHO cells. Biotechnol. Bioeng. 1992, 40:978-990.
33. LaVecchio J.A., Dunne A.D., Edge A.S. Enzymatic removal of alpha-galactosyl epitopes from porcine endothelial cells diminishes the cytotoxic effect of natural antibodies. Transplantation 1995, 60:841-847.
34. Liu B., Spearman M., Doering J., Lattová E., Perreault H., Butler M. The availability of glucose to CHO cells affects the intracellular lipid-linked oligosaccharide distribution, site occupancy and the N-glycosylation profile of a monoclonal antibody. J. Biotechnol. 2014, 170:17-27.
35. Majid F.A.A., Butler M., Al-Rubeai M. Glycosylation of an immunoglobulin produced from a murine hybridoma cell line: the effect of culture mode and the anti-apoptotic gene, bcl-2. Biotechnol. Bioeng. 2007, 97:156-169.
36. Miller W.M., Blanch H.W., Wilke C.R. A kinetic analysis of hybridoma growth and metabolism in batch and continuous suspension culture: effect of nutrient concentration, dilution rate, and pH. Biotechnol. Bioeng. 1988, 32:947-965.
37. Monica T.J., Williams S.B., Goochee C.F., Maiorella B.L. Characterization of the glycosylation of a human IgM produced by a human-mouse hybridoma. Glycobiology 1995, 5:175-185.
38. Munzert E., Mthing J., Büntemeyer H., Lehmann J. Sialidase activity in culture fluid of Chinese hamster ovary cells during batch culture and its effects on recombinant human antithrombin III integrity. Biotechnol. Progr. 1996, 12:559-563.
39. Nyberg G.B., Balcarcel R.R., Follstad B.D., Stephanopoulos G., Wang D.I. Metabolic effects on recombinant interferon-gamma glycosylation in continuous culture of Chinese hamster ovary cells. Biotechnol. Bioeng. 1999, 62:336-347.
40. Ozturk S.S., Palsson B.O. Growth, metabolic, and antibody production kinetics of hybridoma cell culture: 2. Effects of serum concentration, dissolved oxygen concentration, and medium pH in a batch reactor. Biotechnol. Progr. 1991, 7:481-494.
41. Pacis E., Yu M., Autsen J., Bayer R., Li F. Effects of cell culture conditions on antibody N-linked glycosylation-what affects high mannose 5 glycoform. Biotechnol. Bioeng. 2011, 108:2348-2358.
42. Patterson M.K. Measurement of growth and viability of cells in culture. Methods Enzymol. 1979, 58:141-152.
43. Primack J., Flynn G.C., Pan H. A high-throughput microchip-based glycan screening assay for antibody cell culture samples. Electrophoresis 2011, 32:1129-1132.
44. Qian J., Liu T., Yang L., Daus A., Crowley R., Zhou Q. Structural characterization of N-linked oligosaccharides on monoclonal antibody cetuximab by the combination of orthogonal matrix-assisted laser desorption/ionization hybrid quadrupole-quadrupole time-of-flight tandem mass spectrometry and sequential enzy. Anal. Biochem. 2007, 364:8-18.
45. Scallon B.J., Tam S.H., McCarthy S.G., Cai A.N., Raju T.S. Higher levels of sialylated Fc glycans in immunoglobulin G molecules can adversely impact functionality. Mol. Immunol. 2007, 44:1524-1534.
46. Schoen R.C., Bentley K.L., Klebe R.J. Monoclonal antibody against human fibronectin which inhibits cell attachment. Hybridoma 1982, 1:99-108.
47. Sethuraman N., Stadheim T.a. Challenges in therapeutic glycoprotein production. Curr. Opin. Biotechnol. 2006, 17:341-346.
48. Sheeley D.M., Merrill B.M., Taylor L.C. Characterization of monoclonal antibody glycosylation: comparison of expression systems and identification of terminal alpha-linked galactose. Anal. Biochem. 1997, 247:102-110.
49. Shields R.L., Lai J., Keck R., O'Connell L.Y., Hong K., Meng Y.G., Weikert S.H.a., Presta L.G. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity. J. Biol. Chem. 2002, 277:26733-26740.
50. Shinkawa T., Nakamura K., Yamane N., Shoji-Hosaka E., Kanda Y., Sakurada M., Uchida K., Anazawa H., Satoh M., Yamasaki M., Hanai N., Shitara K. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J. Biol. Chem. 2003, 278:3466-3473.
51. Spearman M., Rodriguez J., Huzel N., Sunley K. Effect of culture conditions on glycosylation of recombinant beta-interferon in CHO cells. Cell Technology for Cell Products 2007, 71-85. Springer, Netherlands.
52. Stark N.J., Heath E.C. Glucose-dependent glycosylation of secretory glycoprotein in mouse myeloma cells. Arch. Biochem. Biophys. 1979, 192:599-609.
53. Sutton B.J., Phillips D.C. The three-dimensional structure of the carbohydrate within the Fc fragment of immunoglobulin G. Biochem. Soc. Trans. 1983, 11(Pt 2):130-132.
54. Tachibana H., Taniguchi K., Ushio Y., Teruya K., Osada K., Murakami H. Changes of monosaccharide availability of human hybridoma lead to alteration of biological properties of human monoclonal antibody. Cytotechnology 1994, 16:151-157.
55. Thaysen-Andersen M., Packer N.H. Site-specific glycoproteomics confirms that protein structure dictates formation of N-glycan type, core fucosylation and branching. Glycobiology 2012, 22:1440-1452.
56. Trummer E., Fauland K., Seidinger S., Schriebl K., Lattenmayer C., Kunert R., Vorauer-Uhl K., Weik R., Borth N., Katinger H., Müller D. Process parameter shifting: Part I. Effect of DOT, pH, and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors. Biotechnol. Bioeng. 2006, 94:1033-1044.
57. Tsuchiya N., Endo T., Matsuta K., Yoshinoya S., Aikawa T., Kosuge E., Takeuchi F., Miyamoto T., Kobata A. Effects of galactose depletion from oligosaccharide chains on immunological activities of human IgG. J. Rheumatol. 1989, 16:285-290.
58. Van Berkel P.H.C., Gerritsen J., Perdok G., Valbjørn J., Vink T., Van de Winkel J.G.J., Parren P.W.H.I. N-linked glycosylation is an important parameter for optimal selection of cell lines producing biopharmaceutical human IgG. Biotechnol. Progr. 2009, 25:244-251.
59. Velez-Suberbie M.L., Tarrant R.D.R., Tait A.S., Spencer D.I.R., Bracewell D.G. Impact of aeration strategy on CHO cell performance during antibody production. Biotechnol. Progr. 2012, 29:116-126.
60. Wong D.C.F., Wong K.T.K., Goh L.T., Heng C.K., Yap M.G.S.Y. Impact of dynamic online fed-batch strategies on metabolism, productivity and N-glycosylation quality in CHO cell cultures. Biotechnol. Bioeng. 2005, 89:164-177.
61. Wong N.S.C., Wati L., Nissom P.M., Feng H.T., Lee M.M., Yap M.G.S. An investigation of intracellular glycosylation activities in CHO cells: effects of nucleotide sugar precursor feeding. Biotechnol. Bioeng. 2010, 107:321-336.
62. Wong V.V.T., Nissom P.M., Sim S.-L., Yeo J.H.M., Chuah S.-H., Yap M.G.S. Zinc as an insulin replacement in hybridoma cultures. Biotechnol. Bioeng. 2006, 93:553-563.
63. Wright a Morrison S.L. Effect of C2-associated carbohydrate structure on Ig effector function: studies with chimeric mouse-human IgG1 antibodies in glycosylation mutants of Chinese hamster ovary cells. J. Immunol. 1998, 160:3393-3402.
64. Xing Z., Kenty B.M., Li Z.J., Lee S.S. Scale-up analysis for a CHO cell culture process in large-scale bioreactors. Biotechnol. Bioeng. 2009, 103:733-746.
65. Yang M., Butler M. Effects of ammonia on CHO cell growth, erythropoietin production, and glycosylation. Biotechnol. Bioeng. 2000, 68:370-380.
66. Zanghi J.a., Schmelzer A.E., Mendoza T.P., Knop R.H., Miller W.M. Bicarbonate concentration and osmolality are key determinants in the inhibition of CHO cell polysialylation under elevated pCO(2) or pH. Biotechnol. Bioeng. 1999, 65:182-191.
67. Zhang P., Chan K.F., Haryadi R., Bardor M., Song Z. CHO glycosylation mutants as potential host cells to produce therapeutic proteins with enhanced efficacy. Adv. Biochem. Eng./Biotechnol. 2013, 131:63-87.
68. Zheng K., Bantog C., Bayer R. The impact of glycosylation on monoclonal antibody conformation and stability. mAbs 2011, 3:568-576.
69. Zhu H., Nienow A.W., Bujalski W., Simmons M.J.H. Mixing studies in a model aerated bioreactor equipped with an up- or a down-pumping elephant ear agitator: power, hold-up and aerated flow field measurements. Chem. Eng. Res. Des. 2009, 87:307-317.