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


OBJECTIVE
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.


METHODS
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).


RESULTS
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


CONCLUSIONS
These results suggest that suicide gene-modified tumor cells can act as potent therapeutic vaccines against liver metastasis from colon carcinoma.
Gavelli
A
A
Unité Inserm 364, faculté de médecine, Nice, France.
Baqué
P
P
Mala
M
M
Saint-Paul
M C
MC
Staccini
P
P
Brossette
N
N
Chazal
M
M
Milano
G
G
Gugenheim
J
J
Benchimol
D
D
Bourgeon
A
A
Huguet
C
C
Rossi
B
B
Pierrefite-Carle
V
V
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology*; D043525:Cytosine Deaminase; D004195:Disease Models, Animal; D005437:Flucytosine / Q000008:administration & dosage / Q000627:therapeutic use*; D015316:Genetic Therapy; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary* / Q000628:therapy*; D008297:Male; D009700:Nucleoside Deaminases / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D014611:Vaccination / Q000662:veterinary
D000963:Antimetabolites; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase