Antitumor effect of combined therapy with adenovirus-mediated CD suicide gene and interleukin 2 gene transfer and its immunological mechanism
Ju, D.; Cao, X.; Wang, B.
Zhonghua Zhong Liu Za Zhi 20(2): 108-111
1998
ISSN/ISBN: 0253-3766 PMID: 10920957 Document Number: 484882
Adenovirus harboring E. coli cytosine deaminase gene(AdCD) and adenovirus harboring interleukin 2 gene (AdIL-2) were used for the combined treatment of established tumors in vivo. C57BL/6 mice were inoculated with B16F10 melanoma cells and 3 days later received at the tumor site injections of AdCD and/or AdIL-2 followed by i.p. injection of 5-fluorocytosine (5-Fc) 300 mg/kg per day for 10 days. Mice received combined therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5-Fc, AdIL-2, control adenovirus AdlacZ/5-FC, or PBS. To investigate the immunological mechanism of the antitumor effects of the combined treatment it was found to induce enhanced natural killer cell activity and specific cytotoxic T cell activity. FACS analysis demonstrated that AdIL-2/AdCD/5-Fc therapy increased the expression of H-2Kb and B7-1 on freshly isolated tumor cells. The CD4+ and CD8+ T cell infiltration in the tumor increased significantly. Transfer of CD suicide gene plus 5-Fc combined with transfer of IL-2 gene synergistically inhibits the growth of melanoma in mice. Besides the cytotoxic effect of 5-Fc, specific and non-specific antitumor immunity might be responsible for the therapeutic effect. The combined therapy might have therapeutic potentials for human cancer.