In the present report, antitumor effect of combined transfer of suicide gene and cytokine gene was studied. Adenovirus engineered to express E. Coli. Cytosine deaminase (AdCD) and/or adenovirus engineered to express m...In the present report, antitumor effect of combined transfer of suicide gene and cytokine gene was studied. Adenovirus engineered to express E. Coli. Cytosine deaminase (AdCD) and/or adenovirus engineered to express murine granulocytemacrophage colonystimulating factor (AdGMCSF) were used for the treatment of leukemiabearing mice. The mice were inoculated s.c. with FBL3 erythroleukemia cells and 3 days later received intratumoral injection of AdCD in the presence or absence of AdGMCSF followed by intraperitoneal 5fluorocytosine (5FC) treatment. The results demonstrated that mice received combined therapy of AdCD/5FC and AdGMCSF developed tumors most slowly and survived much longer when compared with mice treated with AdCD/5FC alone, AdGMCSF alone, AdlacZ/5FC or PBS. Combined transfer of CD gene and GMCSF gene achieved higher specific CTL activity than control therapies. Pathological examination illustrated that the tumor mass showed obvious necrosis and inflammatory cell infiltration in mice after combined therapy. The results demonstrated that combined transfer of suicide gene and cytokine gene could synergistically inhibit the growth of leukemia in mice and induce antitumor immunity of the host. The combination therapy might be a potential approach for cancer gene therapy.展开更多
文摘In the present report, antitumor effect of combined transfer of suicide gene and cytokine gene was studied. Adenovirus engineered to express E. Coli. Cytosine deaminase (AdCD) and/or adenovirus engineered to express murine granulocytemacrophage colonystimulating factor (AdGMCSF) were used for the treatment of leukemiabearing mice. The mice were inoculated s.c. with FBL3 erythroleukemia cells and 3 days later received intratumoral injection of AdCD in the presence or absence of AdGMCSF followed by intraperitoneal 5fluorocytosine (5FC) treatment. The results demonstrated that mice received combined therapy of AdCD/5FC and AdGMCSF developed tumors most slowly and survived much longer when compared with mice treated with AdCD/5FC alone, AdGMCSF alone, AdlacZ/5FC or PBS. Combined transfer of CD gene and GMCSF gene achieved higher specific CTL activity than control therapies. Pathological examination illustrated that the tumor mass showed obvious necrosis and inflammatory cell infiltration in mice after combined therapy. The results demonstrated that combined transfer of suicide gene and cytokine gene could synergistically inhibit the growth of leukemia in mice and induce antitumor immunity of the host. The combination therapy might be a potential approach for cancer gene therapy.