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Weapon Against Smallpox Aimed at Cancer

By Steve Mitchell

ScienceNOW Daily News

26 October 2007

A virus that was instrumental in eradicating smallpox is now showing promise as a potential cancer treatment. A genetically engineered strain of vaccinia, better known as the smallpox vaccine, kept rabbits' liver tumors in check in a new study. The virus is now headed toward trials with human patients.

Scientists have been trying to genetically engineer viruses to selectively infect and destroy cancer cells for more than 10 years, but with limited success. The most advanced so far is ONYX-015, a treatment for head and neck cancer based on an adenovirus--the cause of the common cold--that was approved in China in 2005. A team led by Stephen Thorne, a virologist at the University of Pittsburgh in Pennsylvania, decided to see if vaccinia viruses might be better suited for knocking out cancer.

The researchers began by removing two genes from a vaccinia virus that are necessary for its growth in normal cells. Thus, the virus is restricted to growing inside cancer cells, which happen to express high levels of similar genes that the virus can co-opt. The researchers also spliced a gene into the virus that makes it produce granulocyte-macrophage colony-stimulating factor, which induces the body's immune system to recognize and attack tumors infected by the virus.

When the engineered virus was injected into rabbits with tumors in the liver that had spread to the lungs, the liver tumors remained small and the lung tumors shrank, the researchers report online 25 October in the Journal of Clinical Investigation. In animals that did not receive the virus, the liver tumors grew four times larger and new lung tumors appeared. The cancer might be knocked out altogether by higher doses of the virus or combining it with other medications, says Thorne. He has been in discussions with the Food and Drug Administration to start trials of the virus in human patients with any form of solid tumor cancer. Thorne expects trials to begin early next year.

Demonstrating safety will be the first step. Studies with human tissues have indicated that the virus does not infect normal cells, but other safety strategies could include treatments such as vaccinia immune globulin that can counteract rare adverse reactions to vaccinia, he says.

"It's an interesting strategy, and it merits clinical testing," says Louis Weiner, a medical oncologist at Fox Chase Cancer Center in Philadelphia, Pennsylvania. Weiner says that the vaccinia virus may have advantages over ONYX-015, including higher potency against tumors, but he says he is tempering his enthusiasm because animal studies often don't pan out in people.

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