Viral therapy proven safe, shows promise against deadliest brain tumors

james markert webA genetically engineered herpes simplex viral therapy is safe when used with radiation to treat malignant gliomas, one of the most deadly forms of brain cancer, UAB researchers say.

The virus, G207, shown to be safe as a sole therapy in two previous UAB studies, also is safe when combined with low doses of radiation, according to results published in "Molecular Therapy."

Some patients also showed evidence of tumor reduction, and survival rates were increased for others.

“This was a Phase I study designed foremost to see whether the therapy was safe,” said James M. Markert, M.D., Ph.D., professor and chair of UAB's Department of Neurosurgery and the study’s first author.

“While this study, with a limited number of patients and no controls, prevents any conclusions about the efficacy of this treatment, the decrease in tumor size seen on MRI’s in some patients, and an increase in survival in some patients without other proven treatment options, is highly encouraging,” Markert said.

The virus works by infecting tumor cells and replicating until it overwhelms the cell’s machinery and causes the cell to rupture and die, releasing new viral particles. The virus has been genetically modified so that it can reproduce only in tumor cells, which lack the stronger antiviral defense mechanisms of healthy brain cells. After destroying a tumor cell, the virus moves on, looking for new tumor cells to infect.

“While this study, with a limited number of patients and no controls, prevents any conclusions about the efficacy of this treatment, the decrease in tumor size seen on MRI’s in some patients, and an increase in survival in some patients without other proven treatment options, is highly encouraging.”

“Additional studies with modified viruses such as G207 in the treatment of human glioma are certainly warranted from the results of this trial,” Markert said.

Gliomas account for about a third of brain tumors, and survival rates are poor; only about half of the 10,000 Americans diagnosed with malignant glioma survive the first year, and only about one-quarter survive for two years.

UAB is preparing another study with a new modified herpes simplex virus, M032, which preliminary studies indicate could be even more effective. It includes a genetically engineered protein called IL12, which the researchers believe will induce a stronger immune response and will contribute to increased anti-angiogenesis, the process of shutting off the blood supply to tumor cells, denying oxygen and essential nutrients.

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