Virus attacks cancer, spares normal cells.

A mosquito-borne virus isolated 5 decades ago in the Egyptian town of Sindbis could become the latest weapon in the battle against cancer. A seemingly harmless strain of the virus homes in on cancer cells and destroys them, according to a report in the December Nature Biotechnology.

Daniel Meruelo of New York University School of Medicine and his colleagues stumbled upon this unusual medicinal property of the Sindbis virus while seeking to exploit the virus for gene therapy. The original plan was to alter surface proteins of the virus so that it would bind to specific types of cells and shuttle therapeutic genes into them.

In studying a strain of the Sindbis virus stripped of its capability to reproduce, however, the researchers noticed that the strain itself could invade and kill many types of cancer cells growing in lab dishes. No additional gene or alteration was required. What's more, the virus didn't seem to infect most normal cells.

"The virus, on its own, targets tumor cells without us doing anything to it," says Meruelo. "If you inject this into an animal with a tumor, the [virus] will find the tumor cells and kill them, in many cases eradicating the tumor completely."

One year ago, the researchers reported that the Sindbis virus could target cancerous hamster-kidney cells that had been implanted under the skin of mice. In the new study, the virus successfully homed in on and killed the same kind of cancer cells growing in the lungs or pancreas of mice. The virus also rid mice of tumors generated from ovarian cancer cells or pancreatic cancer cells. It even infected cancer cells that had spread, or metastasized, from the initial tumors in the mice.

Sindbis virus can cause fever, headache, and other symptoms in infected people, but any illness usually passes within a week. The weakened strain used by Meruelo's group doesn't cause obvious side effects in treated animals, and there's no evidence that it would cause illness in people.

Meruelo suspects that the virus favors cancer cells because they carry a surface protein called the laminin receptor. Normal cells harbor this receptor, too, but it's usually occupied by the protein laminin. In contrast, many types of cancer cells over-produce the receptor, apparently leaving copies of it free to receive the virus.

It's not yet clear how the virus kills cancer cells, says Meruelo. Biomedical investigators have long sought to slay cancer cells by using viruses that reproduce more readily in cancer cells than in normal ones (SN: 8/19/00, p. 126). Since the viral strain used by Meruelo's team doesn't replicate, it must kill the cells in another manner. Meruelo speculates that the strain could be tested on people with cancer within 2 years.

"What works in a mouse model [of cancer] doesn't necessarily translate into humans," cautions Frank McCormick of the University of California, San Francisco, who has engineered cold viruses that destroy tumors. He notes that a person's immune response may thwart repeated administrations of the Sindbis virus.