Monday, March 03, 2008

A Viral Attack against Brain Tumors

A rabies-related virus seeks out and destroys tumors in the brain.

By Jennifer Chu

A viral view: Researchers at Yale University have genetically engineered a virus (green) that specifically attacks brain tumors in mice (red). The virus kills the primary tumor masses (B) and migrating tumor cells (E), while leaving healthy tissue intact. Credit: Van den Pol/Yale University

This year, more than 21,000 people will be diagnosed with some form of brain cancer, according to the National Cancer Institute. While benign forms are relatively easy to treat, malignant tumors require a combination of surgery, chemotherapy, and radiation. Even then, tumor cells may remain deeply lodged, replicating and spreading quickly through healthy brain tissue.

Now researchers at Yale University have found that a virus that's in the same family as rabies effectively kills an aggressive form of human brain cancer in mice. Using time-lapse laser imaging, the team watched vesicular stomatitis virus (VSV) rapidly home in on brain tumors, selectively killing cancerous cells in its path, while leaving healthy tissue intact. What's more, Anthony Van den Pol, lead researcher and professor of neurosurgery and neurobiology at Yale, says that VSV is able to self-replicate and produce secondary lines of defense.

"A metastasizing tumor is fairly mobile, and a surgeon's knife can't get out all of the cells," says Van den Pol. "A virus might be able to do that, because as a virus kills a tumor cell, it could also replicate, and you could end up with a therapy that's self-amplifying."

In the past few years, scientists have looked to viruses as potential allies in fighting cancer. Researchers at the Mayo Clinic are engineering the measles virus to combat multiple myeloma, a cancer of the bone marrow. And while various groups have seen limited results after injecting herpes and polio-related viruses directly into brain tumors in mice, Van den Pol wanted to find a more effective cancer-killing strain.

His search for a virus candidate began six years ago, when he and his colleagues tested the effect of different viruses on brain tumors in culture. Repeatedly, VSV came out "at the top of the heap." The team grew the virus through many generations, isolating strains that infected cancer cells quickly while having a slow effect on healthy cells. The researchers recently ran the most effective strain through a number of tests in live mice, and they've published their results in a recent issue of the Journal of Neuroscience.

In its experiment, the team transplanted glioblastoma--the most common and aggressive form of human brain cancer--into the brains of mice. Prior to transplantation, researchers genetically engineered the tumor cells to express a red marker, which, once inside the brain, would show up in laser microscopy scans. Similarly, Van den Pol inserted a green marker in VSV cells and injected the virus intravenously through the tail. Within a few days, researchers observed that the green virus found its way to the brain and selectively infiltrated red tumor masses and individual tumor cells, while avoiding normal cells. Van den Pol says that as the virus infects tumors, cancerous cells start to turn green, swelling up until they eventually burst.