Study: Training a Cold to Kill Cancer/Tweak Virus on Tumors

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http://seattlepi.nwsource.com/local/357 ... apy07.html

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By TOM PAULSON

P-I REPORTER

Researchers at the University of Washington and the Fred Hutchinson Cancer Research Center are trying to trick a strain of the cold virus into killing several kinds of cancer, including a notoriously difficult-to-treat brain tumor.

"There are not many options out there for these patients," said Dr. Hans-Peter Kiem at Fred Hutch, noting that most people with this kind of tumor, glioblastoma multiforme, die within a year of diagnosis.

So far, the scientists have only been able to use the viruses to attack the brain tumors in mice.

The concept of employing viruses as biological anti-cancer smart bombs, though it may sound bizarre, has been around for quite a while.

"It's not a new idea," said Dr. Andre Lieber, a researcher at the University of Washington and a leader in this field. But Lieber and others are using innovative genetic techniques to retrain the common cold virus, known as adenovirus.

Some say the notion of enlisting infections to fight cancer first took hold back in 1912, when a rabid dog bit an Italian woman who had advanced ovarian cancer. Italian doctors injected the woman with a weakened rabies virus, a vaccine, to protect her against the deadly infection. And after the immunization, to everyone's surprise, her aggressive ovarian tumor also shrank back.

This is often cited as the first scientific report of the possibility that viral infections or vaccinations might somehow work against cancer. There had been earlier anecdotal stories about people with cancer being cured after getting this or that bug, but not much hard evidence.

"It wasn't until the 1950s and '60s that it really took off," Lieber said. Scientists in the '50s and '60s tried injecting cancer patients with all sorts of live viruses such as mumps or the cold virus, he said, but without really knowing exactly what was going on inside the body.

If you consider what cancer really is and what viruses do, it makes perfect sense. Cancer is the uncontrolled proliferation of cells in the body. Viruses selectively kill cells.

"The trick is to make them kill only the cells you want them to kill, the cancer cells," Lieber said.

Lieber, Kiem and their colleagues have focused on a strain of cold virus, adenovirus serotype 5 (or Ad5). The cold virus achieves its purpose in nature by injecting its genes into our cells, forcing our nasal passage cells or whatever else is infected to produce new viral offspring. Eventually the nose or lung cells that are infected burst, which helps explain why we cough and our noses turns red.

Catching a cold means your cells have been hijacked. Lieber and Kiem, in turn, are hijacking the cold virus to redirect it against cancer.

"Andre has modified the viruses so they can selectively target the tumor cells, replicate inside them and kill them," Kiem said. "And they can only replicate inside the tumor cells."

Though the research is limited to mice in the U.S., Lieber is working with British researchers to do clinical testing soon of his modified cold virus in a dozen people with late-stage, incurable colon cancer.

There are still plenty of obstacles, however, to making this an approved cancer therapy -- beginning with the immune system's tendency to fiercely attack and destroy viruses.

"That's a big problem," Lieber said. One way to get around it, he said, is to use immune-suppressing drugs until the anti-cancer virus finishes its attack on the tumor.

Another concern is that the virus could stimulate an adverse immune response in the patient, he said, or that the altered virus would evolve and revert to its disease-causing natural "wild type" -- or perhaps turn into something even worse.

"Andre is an incredibly creative guy, but he does tend to focus on problems," joked Dr. Stephen Russell, a researcher at the Mayo Clinic in Rochester, Minn., widely considered one of the world leaders in the field known as oncolytic (cancer-killing) virotherapy.

Russell and his team have altered measles viruses to attack ovarian cancer, multiple myeloma and glioblastoma, and have recently launched early stage human trials.

"It's no longer a question of whether virotherapy will work so much as it is a question of what we still need to do to make it work better," Russell said.

After the field's long history of fits and starts, the Mayo Clinic scientist is nevertheless concerned about anything that might once again send this avenue of inquiry back into hibernation.

When his 17-year-old daughter came home one night to report that she just saw the movie "I Am Legend," in which Will Smith is a scientist who alters a measles virus that creates zombies and kills everyone in Manhattan, Russell was concerned.

"I thought, 'Oh no, here we go,' " he said. "We're at a very vulnerable stage in development, just moving into early stage human trials."

Russell and his colleagues monitored the Internet to see what people said about this Hollywood movie that had the altered measles virus creating zombies and depopulating New York City. Fortunately, few saw any reason to storm the Mayo Clinic and demand that the science stop. "It may have helped that the movie was pretty cheesy," Russell said.

Despite his reputed tendency to see most glasses half empty, Lieber believes the new genetic and molecular biological techniques available today do promise to finally make virotherapy an effective, incredibly accurate and safe way to rid the body of cancer.

"These viruses have evolved over millions of years to figure out how to get into cells," he said. "They have an inherent ability to take over specific cells and kill them."

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(Seattlepi.com, By Tom Paulson, PI Reporter, April 6, 2008)

Disclaimer:

The information contained in these articles may or may not be in agreement with my own opinions. They are not posted as medical advice of any kind.