Anti-brain tumor agent derived from herpes virus passes next hurdle

Nov 6 2008

An anti-brain tumor agent developed from a genetically engineered herpes simplex virus has been shown to be safe when given in two doses and injected directly into the brain of patients with malignant glioma.

New research from UAB (University of Alabama at Birmingham) published online in Molecular Therapy, also showed that the drug, G207, appeared to prompt an immune response in patients and showed signs of actively pursuing and killing cancer cells.

UAB researchers studied six patients with recurrent glioblastoma multiforme, one of the most deadly forms of brain cancer. G207 was injected directly into the tumors, which were surgically removed several days later. More of the drug was then injected directly into the brain in the cavity where the tumor had been removed. No major adverse effects were observed, which was the primary goal of the study.

“This was the first test of G207 injected directly into the brain and the results are promising,” said James Markert, M.D., M.P.H, professor and director of neurosurgery and principal investigator in the trial. “The drug appears to be safe when used in two doses and administered directly to brain tissue.”

The drug works by infecting a cancer cell and taking over the cell’s machinery. It then replicates, making thousands of new viruses that overload the cancer cell and kill it. These viruses the search out more cancer cells to infect and the process continues.

“We’re also seeing an immune response from the body,” Markert says. “White blood cells are triggered by the presence of the virus and when they arrive at the tumor, they appear to augment the attack on the tumor cells.”

Markert has been examining the herpes simplex virus as a potential brain cancer therapy since arriving at UAB in 1996 and previously during a fellowship at Massachusetts General Hospital, in Boston. Previous studies have shown the virus only effects tumor cells and is harmless to other cells in the body. Earlier studies of a single dose of G207 delivered to the tumor also showed no adverse effects from the drug.

“The herpes virus has been well studied, its genes are completely sequenced, and it’s large enough to let us put a good supply of foreign genes into it,” Markert said.

“We already have conducted a battery of safety tests and clinical trials using modified herpes virus vectors—and this study confirms the safety of the virus when injected into the brain.”

About half of the 17,000 brain tumors diagnosed in the Unites States each year are malignant glioma, the most severe form of brain tumor. Survival rates are very poor, with as few as 10 percent of patients living for two years. While the new study was primarily looking at safety issues, not survival rates, Markert points out that the median survival rate for the study subjects was 23 months following diagnosis, which provides some indication of the potential for increased survivability following treatment with G207.

The trail was sponsored by MediGene AG and supported in part by the National Cancer Institute.

http://www.uab.edu/