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Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with 5-fluorocytosine suppresses growth of colorectal liver metastases

Gene Therapy volume 8, pages 1241–1247 (2001)Cite this article

Abstract

Targeting of colorectal liver metastases by regional gene therapy was tested in a clinically relevant syngeneic model. First, the CEA-CD-113 retroviral vector containing the cytosine deaminase gene controlled by the CEA specific tumour cell promoter, was shown in vitro to convert 5-fluorocytosine to 5-fluorouracil, resulting in cancer cell killing with a large bystander effect. Second, 10 days after the establishment of liver metastases, retroviral vectors were delivered to the liver by hepatic artery injection. After 5-fluorocytosine administration for 7 days, most surface metastases disappeared and tumour volumes were suppressed up to 8.2-fold. The results support the development of this approach for patient treatment.

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Acknowledgements

We are grateful to John Yates and Gerry Lepts (University of Liverpool) for technical support.

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Authors and Affiliations

  1. Department of Surgery, University of Liverpool, Liverpool, UK

    MJ Humphreys, P Ghaneh, W Greenhalf & JP Neoptolemos

  2. Department of Pathology, University of Liverpool, Liverpool, UK

    F Campbell

  3. UK GlaxoSmithKline Inc., Beckenham, Kent, UK

    TM Clayton & P Everett

  4. GlaxoSmithKline Inc., Research Triangle Park, NC, USA

    BE Huber & CA Richards

  5. GlaxoSmithKline Inc., Stevenage, Hertfordshire, UK

    MJ Ford

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Humphreys, M., Ghaneh, P., Greenhalf, W. et al. Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with 5-fluorocytosine suppresses growth of colorectal liver metastases. Gene Ther 8, 1241–1247 (2001). https://doi.org/10.1038/sj.gt.3301518

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