Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: Evidence of distant bystander effect

The cytosine deaminase gene of Escherichia coli converts the nontoxic compound 5-fluorocytosine into 5-fluorouracil (5-FU), thereby acting as a suicide gene when introduced into cancer cells, killing the cells when they are exposed to 5-fluorocytosine. We analyzed the efficacy of using cytosine deam...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1999-12, Vol.91 (23), p.2014-2019
Main Authors: PIERREFITE-CARLE, V, BAQUE, P, GAVELLI, A, MALA, M, CHAZAL, M, GUGENHEIM, J, BOURGEON, A, MILANO, G, STACCINI, P, ROSSI, B
Format: Article
Language:English
Subjects:
5-fluorouracil
Animals
Antifungal Agents - pharmacology
Antimetabolites - pharmacology
Antineoplastic Agents
Biological and medical sciences
Cancer Vaccines - pharmacology
Cells
Colon cancer
Colonic Neoplasms - pathology
Combined treatments (chemotherapy of immunotherapy associated with an other treatment)
Cytosine Deaminase
Escherichia coli
Escherichia coli - enzymology
Flow Cytometry
Flucytosine - pharmacology
Fluorouracil
Gene therapy
Genetic Therapy
Killer Cells, Natural
Liver
Liver Neoplasms - immunology
Liver Neoplasms - secondary
Liver Neoplasms - therapy
Male
Medical research
Medical sciences
Nucleoside Deaminases - genetics
Pharmacology. Drug treatments
Rats
Transfection
Tumor Cells, Cultured
Tumors
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Summary:The cytosine deaminase gene of Escherichia coli converts the nontoxic compound 5-fluorocytosine into 5-fluorouracil (5-FU), thereby acting as a suicide gene when introduced into cancer cells, killing the cells when they are exposed to 5-fluorocytosine. We analyzed the efficacy of using cytosine deaminase-bearing cancer cells as an autologous tumor vaccine in a rat model that mimics liver metastasis from colon carcinoma. We introduced a plasmid vector containing the E. coli cytosine deaminase gene into a BDIX rat colon carcinoma cell line. Intrahepatic injection of the modified cells in syngeneic animals generates a single experimental liver "suicide tumor." We then analyzed the effect of 5-fluorocytosine treatment in terms of regression of cytosine deaminase-expressing cells in vivo as well as protection against wild-type cancer cells. Treatment with 5-fluorocytosine induced regression of cytosine deaminase-expressing (CD+) tumors, with seven of 11 treated animals being tumor free at the end of 30 days and a statistically significant difference in tumor volumes between treated and control animals (two-sided P
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/91.23.2014