The treatment of glioblastoma multiforme through activation of microglia and TRAIL induced by rAAV2-mediated IL-12 in a syngeneic rat model

Background: microglial cells are the predominant immune cells in malignant brain tumors,but tumors may release some factors to reduce their defensive functions. restoration of the anti-cancer function of microglia has been proposed as a treatment modality for glioblastoma. we examined the effect of intra-cranially administered recombinant adeno-associated virus encoding interleukin-12 (raav2/il12) on transfection efficiency,local immune activity and survival in a rat model of glioblastoma multiforme. methods. f344 rats were injected with raav2/il12 and implanted with syngeneic rg2 cells (glioblastoma cell line). intracerebral interleukin-12 and interferon- concentrations were determined by elisa. activation of microglia was determined by expressions of ed1 and tumor necrosis factor-related apoptosis-inducing ligand (trail) which were evaluated by western blotting and immunohistochemistry. the proliferation of cancer cells was evaluated with ki67 immunohistochemistry and apoptosis of cancer cells with tunel. results: the brains treated with raav2/il-12 maintained high expression of interleukin-12 and interferon- for at least two months. in syngeneic tumor model,brains treated with raav2/il12 exhibited more infiltration of activated microglia cells as examined by ed1 and trail stains in the tumor. in addition,the volume of tumor was markedly smaller in aav2/il12-treated group and the survival time was significantly longer in this group too. conclusion: the intra-cerebrally administered raav2/il-12 efficiently induces long lasting expression of il-12,the greater infiltration of activated microglia cells in the tumor associated improved immune reactions,resulting in the inhibited growth of implanted glioblastoma and the increased survival time of these rats. © 2012 chiu et al; licensee biomed central ltd.