Vaccination by suicide gene therapy against a model of hepatic metastasis from colon cancer in the rat

• Published in: Annales de chirurgie Vol. 125; no. 6; p. 552
• Main Authors: Gavelli, A, Baqué, P, Mala, M, Saint-Paul, M C, Staccini, P, Brossette, N, Chazal, M, Milano, G, Gugenheim, J, Benchimol, D, Bourgeon, A, Huguet, C, Rossi, B, Pierrefite-Carle, V
• Format: Journal Article
• Language: French
• Published: France 01.07.2000
• Subjects: Animals; Antimetabolites - administration & dosage; Antimetabolites - therapeutic use; Colonic Neoplasms - pathology; Cytosine Deaminase; Disease Models, Animal; Flucytosine - administration & dosage; Flucytosine - therapeutic use; Genetic Therapy; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Liver Neoplasms - therapy; Male; Nucleoside Deaminases - administration & dosage; Nucleoside Deaminases - therapeutic use; Rats; Vaccination - veterinary
• ISSN: 0003-3944

Suicide gene therapy consists of transferring into tumor cells a viral or bacterial gene encoding for an enzyme which converts a non-toxic product into a lethal drug. To analyze the therapeutic potential of vaccination with tumor cells expressing the bacterial cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) treatment in a rat liver metastasis model. We used a rat colon carcinoma cell line which, after subcapsular or intraportal injection in syngenic animals, generates single or multiple experimental liver metastases, respectively. We have shown that introduction of a vector expressing the CD gene in this colon carcinoma cell line results in 5-FC sensitivity (PRObCD). Intrahepatic subcapsular injection of PRObCD tumor cells, followed by 5-FC treatment, induces total regression of a wild-type tumor pre-established in the contralateral liver lobe in 45% of animals with a 96% decrease in mean volume (p < 0.0001), demonstrating the existence of a distant bystander effect. This vaccination significantly increased the survival of rats with single (log-rank p < 0.0001) or multiple (log-rank p = 0.01) liver metastasis These results suggest that suicide gene-modified tumor cells can act as potent therapeutic vaccines against liver metastasis from colon carcinoma.