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Virus Engineers: Modifying Herpes to Treat Brain Tumors
This year, more than 17,000 Americans will be diagnosed with brain tumors, and about half of those will be malignant gliomas—one of the most deadly forms of the disease.
UAB Comprehensive Cancer Center researchers, however, are examining new ways to fight these devastating tumors by genetically engineering a common virus to attack and kill cancer cells.
Led by Cancer Center scientist James Markert, M.D., researchers are conducting clinical trials using a modified version of the herpes simplex virus, known for causing cold sores and fever blisters. The altered virus is harmless for normal cells but a potent weapon against tumor cells.
Promising Results
Dr. Markert has been examining the herpes simplex virus as a potential therapy for brain tumors since he joined UAB’s faculty in 1996. He says that as many as 80 percent of adults have been exposed to herpes simplex at some point. Consequently, their bodies have already developed antibodies to the virus. Initial studies conducted about 10 years ago showed that a single dose of the modified virus, called G207, was completely safe when injected directly into the tumors of patients, who showed no adverse effects from the drug. Dr. Markert’s next step was to determine if it was possible to administer more than one dose of the virus—and if it could be delivered to the tumor as well as the surrounding brain.
The results of that study, published in late 2008, revealed promising findings. The study examined six patients with recurrent glioblastoma multiforme whose cancers had progressed despite surgery, chemotherapy and radiation therapy. G207 was first injected directly into the tumor, and after two to five days, the tumor was surgically removed. Another dose of G207 was injected into the brain cavity where the tumor had been located.
Though the primary objective of the study was to determine safety, not survival rates, the patients experienced a median survival rate of 23 months—a significant finding, Dr. Markert says. “Even with radiation and chemotherapy, median survival for these tumors is only 14 1/2 months,” he explains.
G207 works by infecting and replicating within cancer cells, creating thousands of new viruses that eventually overload and kill the tumor. These viruses then search out more cancer cells and continue the process. In addition, Dr. Markert says, “White blood cells are triggered by the presence of the virus and appear to augment the attack on the tumor.”
Stronger by Design
Dr. Markert and his team recently completed a study that paired a dose of G207 virus with a high dose of radiation for other patients whose cancer had returned following standard therapies. The combined treatment was tolerated extremely well, and some patients experienced a “remarkable” response, as if the tumor had been surgically removed, Dr. Markert says.
While the modified herpes virus has produced positive results, researchers are trying to engineer G207 to make it even more effective. Dr. Markert’s team has added a protein called interleukin-12 to the virus to draw white blood cells to attack uninfected tumor cells. Interleukin-12 also makes it tougher for the tumor to sprout new blood vessels.
With funding and additional support from the National Cancer Institute, Dr. Markert hopes to begin the next herpes virus study within the next year. He believes it may lead to dramatic improvements for the more than 350 patients with malignant gliomas who come to the Cancer Center each year.
“While we can remove the majority of the tumor surgically, we necessarily leave tumor cells behind,” Dr. Markert says. “They are quick to mutate and are resistant to radiation, and the blood-brain barrier makes most chemotherapies ineffective. While chemotherapy and radiation can slow these tumors down, we do not yet have a cure.
“It is clear that the herpes simplex virus is an important possible weapon in our battle against these tumors.”
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