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Production of Secretable Proteins Using the Passage In Vivo as Tumours of Cells Carrying Heat-Inducible Expression Constructs

Bio/Technology volume 6, pages 953–958 (1988)Cite this article

Abstract

We have established cell lines that contain plasmid constructs carrying combinations of genes coding for human growth hormone (hGH) or the human hepatitis B virus surface antigen complex (HBsAg), placed under the expression control of a human heat shock promoter. In addition, neomycin resistance genes and oncogenes have been employed for selection of cell lines. These lines have been passed as tumours in rodents. After proteolytic dissociation of cells from excised tumours, up to 109 tumour cells were obtained in culture, per (20 mm diameter) tumour. These cells can produce, after heat induction, approximately similar quantities of hGH or HBsAg as the parental cells prior to passage as tumours in animals. In addition, we have cultivated one of these cell lines on spherical microcarriers (cytodex 1R) in 1 liter fermentors, using media with or without serum. Under these conditions, a daily production of mg quantities of hGH per tumour, per heat shock, was obtained. This procedure is applicable to the pilot scale production of natural proteins, or their protein-engineered variants.

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Authors and Affiliations

  1. Intracel S.A., Department of Genetic Engineering, 7, route de Drize, CH-1227, Carouge-Geneva

    Michel Dreano, Chantal Salina & Peter Bromley

  2. Laboratoire de Biochimie Médicale, Faculté de Médecine, 7, bd Jeanne-d'Arc, F-21033, Dijon

    Michel Fischbach, Frederic Montandon & Prudent Padieu

Authors
  1. Michel Dreano
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  2. Michel Fischbach
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  3. Frederic Montandon
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  4. Chantal Salina
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  5. Prudent Padieu
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  6. Peter Bromley
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Dreano, M., Fischbach, M., Montandon, F. et al. Production of Secretable Proteins Using the Passage In Vivo as Tumours of Cells Carrying Heat-Inducible Expression Constructs. Nat Biotechnol 6, 953–958 (1988). https://doi.org/10.1038/nbt0888-953

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