combined interleukin 12 and granulocyte-macrophage colony-stimulating factor gene therapy synergistically suppresses tumor growth in the murine fibrosarcoma

Background: interleukin (il-12) and the granulocyte-monocyte colony-stimulating factor gene (gm-csf) have been used as immunotherapeutic agents in cancer gene therapy as they activate dendritic cells and boost anti-tumor immune responses. il-12 and gm-csf have different roles in anti-tumor immune response. objectives: the aim of present study was to investigate the anti-tumor effects of combined gene therapy with gm-csf and il-12 in a fibrosarcoma mouse model. methods: to investigate the combined therapeutic effect of gm-csf and il-12, wehi 164 tumor cells were transfected with murine gm-csf (m-gm-csf) and murine il-12 (m-il-12) genes, using lipofectamine. the fibrosarcomamousemodelwas established by subcutaneous injection of transfected cells to balb/c mice. mice were sacrificedandthe tumors were extracted. tumorsizes were measured by caliper. the expression of gm-csf, il-12 and ifn- was studied by real-time pcr and immunoblotting. the expression of ki-67 (a proliferation marker) in tumor masses was studied by immunohistochemistry staining. results: the tumor size was reduced in il-12 + gm-csf group (p < 0.0001); the results of western blotting and real-time pcr demonstrated that il-12, gm-csf and ifn- expression increased in il-12+gm-csf group (with a relative expression of: 2.86, 1.98, and 2.560). immunohistochemistry staining indicated that ki-67 expression was reduced in il-12 + gm-csf group. conclusions: combination therapy with gm-csf and il-12 displayed significant therapeutic effects and represented a promising gene therapy strategy for cancer.