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Turning Fearsome Viruses Into Cancer Foes

Scientists are using herpes, measles bugs to destroy malignant cells

WEDNESDAY, April 20, 2005 (HealthDay News) -- Transforming an old medical enemy into a new friend, researchers are using genetic engineering to draft viruses into the war against cancer.

Preliminary results from one study suggest that a modified version of the herpes simplex virus can be harnessed to halt the spread of tumor cells in patients suffering from malignancies of the skin, breast, head, neck or colon.

And in a second study, researchers are manipulating the common measles virus to destroy liver cancer cells.

"The general idea of using viruses to destroy tumor cells is extremely early in its development, but it has the potential for being very useful," said Dr. Theodore Friedmann, director of the Program in Human Gene Therapy at the University of California-San Diego.

Both studies were reported this week at the American Association for Cancer Research annual meeting, in Anaheim, Calif.

As study author and clinical research fellow at Hammersmith Hospital, Imperial College in London, Jennifer Hu leads a lab team that is exploring the potential of "OncoVEX" -- a re-engineered herpes cold sore virus, recently developed by the British-American biotech company, Biovex Ltd.

In a press release, the researchers claim that OncoVEX is more potent than a regular herpes virus, enabling it to operate as an effective "oncolytic" -- or cancer-killing -- agent. The engineered virus is designed to target only harmful cancer cells, leaving the surrounding healthy tissue intact.

Scientists further reconfigured the virus by inserting an extra immune-stimulating gene, called GM-CSF, into its DNA. By adding the gene, the virus stimulates the body's own natural immune defenses into attacking stray tumor cells that might survive initial treatment with the virus. In this way, they hope to reduce the threat that localized cancers might spread to other body parts.

To date, Hu and her colleagues have conducted preliminary clinical trials using OncoVEX in 26 British patients afflicted with late-stage skin, breast, head, neck or colorectal cancers.

Two weeks after injecting anywhere from one to three doses of the modified herpes virus directly into the tumors, biopsies displayed evidence of "considerable" cancer cell destruction among all the various types of cancers.

According to the researchers, these findings suggest the addition of the GM-CSF gene is initiating the hoped-for protective immune response.

Also reported at the meeting was a second early study focusing on the possibility that a modified measles virus -- known as MV-Edm -- might be similarly used to treat liver cancer.

Patients currently diagnosed with this disease have a relatively poor survival rate, with nearly 1 million people worldwide succumbing to the illness each year.

"The preliminary data looks very promising," said study author Dr. Boris Blechacz, a research fellow in the Molecular Medicine Program at the Mayo Clinic in Rochester, Minn.

"Primary liver cancer has a bad prognosis," Blechacz noted. "Surgery is the most common treatment, but for curative therapy just 12 percent of patients qualify for surgery. The rest choose chemotherapy, but in the end the problem is that liver cancer gets diagnosed too late most of the time. So, we're looking into this as a therapeutic option in addition to surgery and chemotherapy."

After finding that liver cancer cells contain large quantities of the receptors to which the measles virus is naturally drawn, Blechacz and his team extracted liver tumor tissue samples from patients and injected them with MV-Edm in a laboratory setting.

In addition, the researchers grafted human liver cancer samples onto laboratory mice, then treated the mice with the engineered measles virus.

The authors report that large-scale cancer cell death was evident in both cases, noting that the tumors were fully eradicated in nearly one-third of the mice. The engineered measles virus appears to jump-start a natural process called apoptosis, or programmed cell death, causing a kind of mass suicide of cancer cells.

Blechacz and his colleagues then went one step further. First, they attached an iodine "transport" protein to the engineered measles virus, then introduced this MV-Edm/protein combination into mouse liver tumors. According to the Mayo team, the added iodine protein should act as a magnet for subsequent radioactive iodine injections.

The strategy succeeded. As hoped, tumor cells injected with the measles virus and radioactive iodine displayed a high degree of radioactive iodine absorption. According to Blechacz' group, this could open the door to highly-targeted measles virus treatments used in combination with radioactive iodine.

"We were surprised about the strength with which these therapies worked, how efficiently they worked," said Blechacz. "But it's really too early to see this as a therapeutic option. We calculate that this might develop at least another two years from now."

Friedmann agreed that only time -- and much more research -- will determine just how effective these therapies turn out to be.

"Certainly the approach is appealing, and from what I've heard so far the results are interesting and deserve a lot of further work," he said.

Friedmann expressed enthusiasm for the concept of narrowly targeting tumor cells with safely modified viruses, given that current cancer treatments tend to throw the baby out with the bathwater.

"Killing cancer with drugs such as [systemic] chemotherapy -- as effective as it is -- is a very blunt approach that uses very harmful drugs which affect many parts of the body in addition to the cancer itself," he noted. "That's why people have such a hard time with the side effects. So, I think this approach does hold promise."

More information

For more on gene therapy and cancer treatment, check out the National Cancer Institute .

SOURCES: Boris Blechacz, Ph.D., research fellow, Molecular Medicine Program, Mayo Clinic, Rochester, Minn.; Theodore Friedmann, M.D., director, Program in Human Gene Therapy, University of California-San Diego; April 19, 2005, presentations, American Association for Cancer Research annual meeting, Anaheim, Calif.
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