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Growth rate suppression of cultured mammalian cells enhances protein productivity

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Cell Culture Engineering IV

Part of the book series: Current Applications of Cell Culture Engineering ((CACC,volume 1))

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Abstract

Suppression of proliferation of cells which contain stable or stabilized mRNA coded for a protein to be produced, a partial mimic of cell differentiation, was examined for enhancing protein production by cultured mammalian cells. Hybridoma 2E3 cells which were adapted to be interleukin-6 sensitively growth-suppressed accumulated the mRNA of IgG1 which is reported stable, and IgG1 production rate increased as a result when their growth was suppressed with interleukin-6. A myeloma cell line was similarly adapted; the obtained myeloma cells can be used as host cells for enhancing production of exogenous proteins by suppressing growth with interleukin-6. Temperature-sensitively growth-suppressible mutants of mouse mammary carcinoma FM3A were transfected with cDNA of IgM λ1 chain and cultured at nonpermissive temperature to enhance production of λ1. Addition of various growth-suppressive reagents to culture medium was studied for finding methods suitable for suppressing growth while maintaining high cell viability. Caffeine yielded the best results among these reagents. Deprivation of various growth-supporting components in culture medium was also tested; simultaneous deprivation of insulin and transferrin viably suppressed growth of hybridoma 2E3 cells, resulting in enhanced antibody productivity.

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Abbreviations

IL6:

recombinant human interleukin-6

TGF:

β-recombinant human TGF-β1

X63.653-P3X63:

Ag8.653 myeloma

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© 1994 Springer Science+Business Media Dordrecht

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Takahashi, K., Tereda, S., Ueda, H., Makishima, F., Suzuki, E. (1994). Growth rate suppression of cultured mammalian cells enhances protein productivity. In: Buckland, B.C., Aunins, J.G., Bibila, T.A., Hu, WS., Robinson, D.K., Zhou, W. (eds) Cell Culture Engineering IV. Current Applications of Cell Culture Engineering, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0257-5_7

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  • DOI: https://doi.org/10.1007/978-94-011-0257-5_7

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-4114-0

  • Online ISBN: 978-94-011-0257-5

  • eBook Packages: Springer Book Archive

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