Viral oncolysis of glioblastoma

The current state of replication-competent or replication-selective oncolytic viral treatment of malignant astrocytomas is reviewed. This includes studies examining the DNA viruses herpes simplex type I and adenovirus, both of which can be engineered to replicate only in dividing cancer cells, and RNA viruses, including reovirus, measles virus, Newcastle disease virus (NDV), and vesicular stomatitis virus (VSV), some of which replicate selectively in brain tumors because of transformed cellular defects in antiviral immunity and others which require modification to render them nonpathogenic in health brain tissue while destroying resident tumor cells. Also discussed is that local viral expression of cytokines could overcome the immunosuppressive tumor microenvironment and lead to tumor clearance including immune clearance of distant noninfected tumor cells. We review efforts to engineer DNA and RNA viruses that can selectively infect glioma cells and maintain the ability to replicate within and destroy tumors while being safe for direct injection into the brain or for systemic delivery. A number of oncolytic viruses have been examined in clinical trials, and safety, to date, has been the rule. Nevertheless, we must continually consider in which ways these vectors can be made safer for use in humans. Ultimately, effective treatment of malignant brain tumors may require a multipronged approach; therefore, as trials using oncolytic viruses are completed, it will become necessary to integrate these treatments both with established therapies such as radiation and chemotherapy, as well as with new ones such as angiogenesis inhibitors and immune modulators. The inclusion of tissue-specific promoters within these constructs and the insertion of genes for immune modulation or antiangiogenic molecules are other approaches that will be important to consider in combination clinical trials. With exercise of proper caution, continued development of the field of oncolytic viruses for the treatment of glioblastoma has great promise as an avenue toward effective therapy for these deadly tumors.