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. 2001 Aug;8(16):1241-7. doi: 10.1038/sj.gt.3301518.


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.

MeSH terms

  • Animals
  • Antimetabolites / therapeutic use
  • Carcinoembryonic Antigen / genetics
  • Carcinoma / therapy*
  • Colonic Neoplasms / therapy*
  • Cytosine Deaminase
  • Flucytosine / therapeutic use
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Hepatic Artery
  • Injections, Intra-Arterial
  • Injections, Intraperitoneal
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy*
  • Male
  • Models, Animal
  • Neoplasm Transplantation
  • Nucleoside Deaminases / genetics*
  • Promoter Regions, Genetic
  • Rats
  • Retroviridae / genetics
  • Tumor Cells, Cultured


  • Antimetabolites
  • Carcinoembryonic Antigen
  • Flucytosine
  • Nucleoside Deaminases
  • Cytosine Deaminase