Malignant gliomas are the most common primary tumors in the central nervous system. Despite many efforts to develop effective therapies, the survival rate for patients with malignant gliomas remains poor. In the brain, most of the cells are differentiated and stop undergoing cell division, and only tumor cells tend to grow vigorously in patients with malignant tumors. Gene therapy for this disease using retroviral vectors is thus quite attractive since DNA reverse transcribed from the virus genome can integrate into the host chromosomes during mitosis. Suicide-gene therapy by retrovirus vectors producing HSVtk and the administration of GCV thus has the ability to kill tumor cells in vivo. Packaging cells producing HSVtk-harboring retroviruses were injected into the tumor cavities in clinical trials. A partial regression of tumors was observed, but a recurrence of the glioma occurred even though most of the tumor had previously disappeared. The major problem with the treatment is that the transduction rate is too low to eliminate all the tumor cells, most likely due to an insufficient titer of the virus and to the instability of the injected cells in the lesion. To improve the efficacy of such gene therapy for malignant gliomas, the establishment of methods providing high-titer retrovirus vectors, improving the therapeutic schedule and ensuring the safety of normal tissue are all absolutely imperative. In an animal model, gene therapy by the direct inoculation of a high-titer retrovirus was found to successfully eradicate the tumors. However, such success has so far only been observed in clinical trials. This review provides an update on the state of current gene therapy for malignant gliomas using retroviral vectors.
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