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

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