Adenovirus-mediated combined suicide gene and interleukin-2 gene therapy for the treatment of established tumor and induction of antitumor immunity.
The antitumor effect of the combined transfer of a suicide gene and a cytokine gene was evaluated in the present study. Adenoviruses expressing Escherichia coli cytosine deaminase (AdCD) and adenoviruses expressing murine interleukin-2 (AdIL-2) were utilized for the treatment of established tumors. The mice were inoculated s.c. with FBL-3 erythroleukemia cells and 3 days later received an intratumoral injection of AdCD in the presence or absence of AdIL-2 followed by intraperitoneal 5-fluorocytosine (5-FC) administration. The results demonstrated that tumor-bearing mice treated with AdCD/5-FC in combination with AdIL-2 showed more potent inhibition of tumor growth and survived much longer than did mice treated with AdCD/5-FC, AdIL-2, adenovirus expressing beta-galactosidase/5-FC or phosphate-buffered saline. The tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD4+ and CD8+ T cells infiltrating the tumor after combined therapy. The splenic natural killer and cytotoxic T lymphocyte activities increased significantly in the mice after combined therapy with AdCD/5-FC/AdIL-2. Our results demonstrate that therapy combining a suicide gene and IL-2 gene can inhibit the growth of established tumors in mice significantly and induce antitumor immunity of the host efficiently.
Ju
D W
DW
Department of Immunology, Second Military Medical University, Shanghai, PR China.
Wang
B M
BM
Cao
X
X
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use*; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D005437:Flucytosine / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D009700:Nucleoside Deaminases / Q000096:biosynthesis / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D007376:Interleukin-2; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase