Augmentation of antitumor effect of adenovirus-mediated CD suicide gene therapy by cotransfer of interleukin 2 gene in melanoma-bearing mice.
OBJECTIVE
To investigate the antitumor effect of combined adenovirus encoding E. coli cytosine deaminase (AdCD) and adenovirus encoding murine interleukin 2 (AdIL-2) on murine melanoma.


METHODS
C57BL/6 mice were inoculated s.c. with B16F10 melanoma cells and 3 days later received injections of AdCD and/or AdIL-2 at the site of tumor inoculation followed by administration of 5-flurocytosine (5FC) 300 mg/kg per day for 10 days.


RESULTS
Mice receiving AdCD/5FC/AdIL2 therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5FC, AdIL2, AdlacZ/5FC, or PBS. Immunological analysis illustrated that combined treatment could enhance NK activity and CTL activity. Flow cytometry demonstrated that AdCD/5FC/AdIL2 therapy increased the expression of MHC-1 and CD80 molecules on freshly isolated tumor cells. The CD4+ and CD8+ T cell infiltration in the tumor increased significantly after the combined therapy.


CONCLUSIONS
Our data showed that combined transfer of CD suicide gene and IL-2 gene could inhibit the tumor growth more significantly. The increased specific and non-specific antitumor immunity might be responsible for the enhanced therapeutic effect.
Ju
D W
DW
Department of Immunology, Second Military Medical University, Shanghai 200433, China.
Cao
X
X
Tao
Q
Q
Wang
B
B
Chen
G
G
Yu
Y
Y
D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D005437:Flucytosine / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D007376:Interleukin-2 / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000627:therapeutic use
D007376:Interleukin-2; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase