Therapeutic effect of combined treatment with CD suicide gene and GM CSF gene on murine melanoma and its immunological mechanism

Objective To observe the therapeutic effect of adenovirus expressing cytosine deaminase (AdCD) in combination with adenovirus expressing GM CSF (AdGMCSF) followed by administration of a kind of prodrug, 5 fluorocytosine (5FC) on melanoma in mice. Methods Melanoma bearing mice were administered with AdCD/5FC/AdGMCSF, AdCD/5FC, AdGM CSF, control adenovirus AdlacZ/5FC, or PBS. Results The results demonstrated that significant growth inhibition of established tumors and prolongation of survival period were observed in tumor bearing mice after AdCD/5FC/AdGMCSF combined therapy when compared with mice treated with AdCD/5FC, AdGM CSF, AdlacZ/5FC, or PBS ( P 0.01). The activity of cytotoxic T lymphocytes could be induced significantly after the combined therapy. The expression of MHC I and B7 1 molecules on freshly isolated tumor cells after combined therapy increased greatly, and more dendritic cells and CD8 + T cells infiltrated into the tumor mass when measured with FACS. Conclusion Our results suggest that combined therapy with suicide gene and GM CSF gene transfer could directly eradicate established tumors and efficiently induce the antitumor immunity of the mice.