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Production of recombinant proteins in serum-free media

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Abstract

The advantages of serum-free culture for the manufacture of recombinant biopharmaceuticals from mammalian cells are reviewed. The process favoured is fed-batch serum-free cell culture. This process is applicable to the majority of cell lines, is practical on the large scale, gives the lowest manufacturing cost, and can b e carried out without the use of any serum.

Abstract

The advantages of serum-free culture for the manufacture of recombinant biopharmaceuticals from mammalian cells are reviewed. The process favoured is fed-batch serum-free cell culture. This process is applicable to the majority of cell lines, is practical on the large scale, gives the lowest manufacturing cost, and can be carried out without the use of any serum.

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References

  • Arathoon WR and Birch JR (1985) Large scale cell culture in biotechnology. Science 232: 1390–1395.

    Google Scholar 

  • Avgerinos GC, Drapeau D, Socolow JS, Mao J-I, Hsiao K and Broeze RJ (1990) Spin filter perfusion system for high density cell culture: production of recombinant urinary type plasminogen activator in CHO cells. Bio/technology 8: 54–58.

    Google Scholar 

  • Barnes D and Sato G (1980) Serum-free cell culture: a unifying approach. Cell: 22: 649–655.

    Google Scholar 

  • Bebbington C and Hentschel C (1985) The expression of recombinant DNA products in mammalian cells. Trends Biotechnol. 3: 314–317.

    Google Scholar 

  • Carter MJ, Facklam TJ, Long PC, and Scotland PA (1988) Are continuous cell lines safe as substrates for human drugs and biologics? A case study with human growth hormone. Develop. Biol. Standard 70: 101–107.

    Google Scholar 

  • Cockett MI, Bebbington, CR and Yarranton CT (1990) High level expression of Tissue inhibitor of metalloproteinase in Chinese Hamster Ovary cells using glutamine synthetase amplification. Biotechnology (in press).

  • Davis JM, Arakawa T, Strickland TW and Yphantis DA (1987) Characterisation of recombinant human erythropoiet in produced in Chinese Hamster Ovary cells. Biochemistry 26: 2633–2638.

    Google Scholar 

  • Faure T, Meulien P, Kolbe HVJ, Mignot C and Pavirani A (1989) Engineering Foundation Conferences, New York, USA. The Development of expression systems for production of recombinant proteins in CHO cells: an example recombinant FV111. Cell Culture Engineering II p. 79.

  • Field R, Cockett M and Froud, SJ (1989) In: RE Spier, JB Griffiths, J Stephenne, PJ Crooy (eds.) Advances in Animal Cell Biology and Technology for Bioprocesses, pp. 195–197. Butterworths, Glutamine synthetase amplification of TIMP expression in CHO cells.

  • Field RP, Brand H, Renner GL, Robertson HA and Boraston R (1990) To be presented at European Society of Animal Cell Culture Technology meeting, May 1990. Production of chimeric antibody for tumour imaging and therapy from recombinant Chinese Hamster Ovary and myeloma cells (in press).

  • Friedman JS, Cofer GL, Anderson CL, Kushner JA, Gray PP, Chapman GE, Stuart MG, Lazarus L, Shine J and Kushner PJ (1989) High expression in mammalian cells without amplification. Bio/technology 7: 359–362.

    Google Scholar 

  • Ham RG (1965) Clonal growth of mammalian cells in chemically defined synthetic media. Proceedings of National Academy of Sciences, USA 53: 288–293.

    Google Scholar 

  • Hayter PM, Furlotte D, Wilcox M, Curling EMA, and Jenkins N (1989) In: RE Spier, JB Griffiths, J Stephanne, PJ Crooy (eds.) Advances in Animal Cell Biology and Technology for Bioprocess, pp. 280–282. Butterworths. Recombinant Gamma-Inteferon production by CHO cells in serum-free medium.

  • Higuchi K (1973) Cultivation of animal cells in chemically defined media, a review. Adv. Appl. Microbiol. 16: 111–136.

    Google Scholar 

  • Himmelfarb P, Thayer PS and Martin HE (1969) Spin filter culture: The propagation of mammalian cells in suspension. Science 164: 555–557.

    Google Scholar 

  • Karkare SB, Dean RCJr and Venkatasubramanian KJ (1985) Continuous fermentation with fluidized slurries of immobilized microorganisms. Bio/technology 3: 247–2.

    Google Scholar 

  • Kaufman RJ, Wasley LC, Furie BC and Shoemaker CB (1986) Expression, purification, characterisation of recombinant γ carboxylated Factor IX synthesized in Chinese Hamster Ovary Cells. J. Biol. Chem. 261: 9622–9628.

    Google Scholar 

  • Kenten J and Boss M (1985) Patent Application GB 86/00187, 4/1/85.

  • Kluft C, van Wezel AL, van der Velden CAM, Emeis JJ, Verheien JH and Wijngaards G (1983) In: Advances in Biotechnological Processes 2: 97–111. Large scale production of extrinsic (tissue type) plasminogen activator from human melanoma cells.

  • Knazek RA, Gullino PM, Kohler PO and Dedrick RC (1982) Cell culture on artificial capillaries. Science 178: 65.

    Google Scholar 

  • Lin F-K (1984) European Patent Application 0148605. Production of Erythropoietin.

  • Lubiniecki A, Arathoon R, Plastri G, Thomas J, Wiebe M, Garnick R, Jones A, van Reis R and Builder S (1989) In: RE Spier, JB Griffiths, J Stephenne, PJ Crooy (eds.) Advances in Animal Cell Biology and Technology for Bioprocesses, pp. 442–449. Butterworths. Selected strategies for manufacture and control of recombinant tissue plasminogen activator prepared from cell cultures.

  • McCormick F, Trakey M, Innis M, Dieckmann B and Ringold G (1984) Inducible expression of amplified human beta interferon genes in CHO cells. Molecular Cellular Biology 4: 166–172.

    Google Scholar 

  • Michel M-L, Sobczak E, Malpiece Y, Tiollais P and Shriek RE (1985) Expression of amplified hepatitis B virus surface antigen genes in Chinese Hamster Ovary Cells. Biotechnology 3: 561–566.

    Google Scholar 

  • Mignot G, Ganne V, Faure T and van de Pol H (1989) Engineering Foundation Conferences, New York, USA. Production of recombinant von Willebrand factor in serum free culture by CHO cells grown on porous gelatin microcarriers. Cell Culture Engineering 11: p. 51.

    Google Scholar 

  • Murata M, Eto Y and Shibai H (1988) Large-scale production of Erythroid Differentiation Factor (EDF) by gene-engineered Chinese Hamster Ovary (CHO) cells in suspension-culture. J. Fermentation Technology 66: 501–507.

    Google Scholar 

  • Nguyen C, Rouchouse J and Pouradier-Duteil X (1989) In: RE Spier, JB Griffiths, J Stephenne, PJ Crooy (eds.) Advances in Animal Cell Biology and Technology for Bioprocesses, pp. 65–67. Butterworths. Contamination of Foetal Bovine Serum by Bovine Diarrhea Virus (BVD or MDV) and other related Pestiviruses.

  • Pavirani A, Meulien P and Hamer H, Schamber F, Dolf K, Villeval D, Cordier Y, Wiesel M-L, van de pol H, Piquet Y, Cazanove H-P and Le Coq J-P (1987) Choosing a host cell for active recombinant factor VIII production using vaccinia virus. Biotechnology 5: 389–392.

    Google Scholar 

  • Pennica D, Kohr WJ, Harkins RN, Vehar GA, Ward CA, Bennett WF, Yelverton E, Seeburg PH, Heyneker HL and Goeddel DV (1983) Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 301: 214–221.

    Google Scholar 

  • Reddy VB, Garramone AJ, Sasak H, Wei C, Watkins P, Galli J and Hsiung N (1985) Expression of human uterine tissue-type plasminogen activator in mouse cells using BPV vectors. DNA 6: 461–472.

    Google Scholar 

  • Rhodes M and Birch J (1988) Large-scale production of proteins from mammalian cells. Bio/technology 6: 518–523.

    Google Scholar 

  • Rhodes PM (1989) In: RE Spier, JB Griffiths, J Stephanne, PJ Crooy (eds.) Advances in Animal Cell Biology and Technology for Bioprocesses, pp. 472–474. Butterworths. Recombinant antibodies from CHO cells.

  • Sano E, Sawada R, Kasama K, Shimizu H and Kobayashi S (1989) Constitutive long term production of interferongamma by recombinant mouse C127 cells in serum-free medium—mouse C127 cell culture immobilized on microcarrier. J. Interferon Research 9: Suppl. 2, 5195.

    Google Scholar 

  • Schimke RT (1984) Gene Amplification in cultured animal cells. Cell 37: 705–713.

    Google Scholar 

  • Takazawa T, Takashiki M, Hamamoto K and Murakami H (1988) High cell density perfusion culture of hybridoma cells recycling high molecular weight components. Cytotechnology 1: 171–178.

    Google Scholar 

  • Wagner R, Craft HJ and Lehmann J (1989) In: RE Spier, JB Griffiths, J Stephanne, PJ Crooy (eds.) Advances in Animal Cell Biology and Technology for Bioprocesses, pp. 374–376. Butterworths. The production of human interleukin 2 by recombinant mammalian cells.

  • Wirth M, Li S-Y, Lechmann J, Zettlmeissl G and Hauser H (1989) In: RE Spier, JB Griffiths, J Stephenne, PJ Crooy (eds.) Advances in Animal Cell Biology and Technology for Bioprocesses, pp. 44–50. Butterworths. Screening for and fermentation of high producer cell clones from recombinant BHK cells.

  • Wyatt DE and Dilling RR (1989) In: RE Spier, JB Griffiths, J Stephenne, PJ Crooy (eds.) Advances in Animal Cell Biology and Technology for Bioprocesses. Butterworths. Significance of raw material screening for custom-designed cell culture media.

  • Zebtlemeissel G, Ragg H and Karges HE (1987) Expression of biologically active human antithrombic III in Chinese Hamster Ovary Cells. Biotechnology 5: 720–725.

    Google Scholar 

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Broad, D., Boraston, R. & Rhodes, M. Production of recombinant proteins in serum-free media. Cytotechnology 5, 47–55 (1991). https://doi.org/10.1007/BF00365533

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