Herpes simplex virus thymidine kinase (HSV tk) gene therapy combined with ganciclovir (GCV) medication is a potential new method for the treatment of malignant glioma. We have used both retrovirus-packaging cells (PA317/tk) and adenoviruses (Adv/tk) for gene therapy for malignant glioma. Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients. As a control group, seven tumors in seven patients were transduced with lacZ marker gene 4-5 days before tumor resection. Safety and efficacy of the gene therapy were studied with clinical evaluation, blood and urine samples, MRI follow-up, and survival of the patients. Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction. Frequency of epileptic seizures increased in two patients. No other adverse events possibly related to gene therapy were detected. In the retrovirus group, all treated gliomas showed progression by MRI at the 3-month time point, whereas three of the seven patients treated with Adv/tk remained stable (p < 0.05). Mean survival times for retrovirus, adenovirus, and control groups were 7.4, 15.0, and 8. 3 months, respectively. The difference in the survival times between the adenovirus and retrovirus groups was significant (p < 0.012). It is concluded that HSV tk gene therapy is safe and well tolerated. On the basis of these results further trials are justified, especially with adenovirus vectors.

The treatment for high-grade glioma remains an enigma. The standard treatment using surgery, radiation therapy and chemotherapy for such highly malignant lesions has only yielded modest results, in terms of survival and improving the quality of life of patients. Less than 10% of such patients survive beyond two years. All conventional therapies have failed to increase the survival beyond this extent. There has been a growing interest in the molecular approaches for the treatment of high-grade gliomas which include gene therapy, oncolytic virotherapy, and immunotherapy. These new therapies are in preclinical and investigational stages. They may not substitute the conventional therapies; they may not be the ultimate elixir for this deadly disease. However, in the coming years, they are likely to have synergistic and complimentary roles alongside conventional therapies. Through this paper, we have attempted to highlight the rationale behind gene therapy which can be used for cytotoxic approaches, immunomodulation strategy, and targeted toxin delivery in the tumor cell. We have reviewed current available literature and through this paper focus on reporting such therapeutic options, their potential usage, benefits and limitations.