In cancer war, viruses can be good guys

McClatchy NewspapersJune 23, 2008 

A microscopic view of a reovirus, one of a set of viruses that has been engineered to attack cancer cells but leave normal cells alone.

ONCOLYTICS BIOTECH / CDC / MCT

WASHINGTON — Viruses aren't always the bad guys. Sure, they can cause colds, measles, AIDS and other miseries. But with some tinkering, these tiny organisms may become a new and better way to treat cancer.

In the last few years, scientists have been genetically engineering various viruses so they attack cancer cells but leave healthy cells alone. These "oncolytic" — cancer-destroying — viruses are being tested in hundreds of terminally ill patients for whom surgery, radiation and chemotherapy have failed.

Several of these experimental viruses target malignant brain tumors, like the incurable glioma that's afflicting Sen. Edward Kennedy, D-Mass.

"The past two years have seen several major advances in oncolytic virotherapy," David Kirn, the president of Jennerex Biotherapeutics Inc., a biotechnology firm in San Francisco, reported in the journal Gene Therapy in April. "A large number of clinical trials have been carried out. Safety in humans has been demonstrated in more than 800 patients."

So far, no cancer-killing virus has received U.S. government approval for general use in humans, but dozens of clinical trials are under way to determine their safety and effectiveness.

Some could be ready for doctors to use in the next two or three years, said Dr. Frank McCormick, a cancer researcher at the University of California in San Francisco. He cautioned, however, that many hurdles remain to be overcome before viral therapy will be part of usual medical practice.

Ways must be found to defeat the body's natural immune system, which is primed to destroy invading viruses. Early results show that viruses can shrink a local tumor, but stopping cancer from spreading, or metastasizing, is much harder, McCormick said.

"The real need is systemic treatment for metastatic disease," McCormick said. "We're not there yet with this technology."

Despite the doubts, at least six species of viruses are candidates for cancer therapy.

For example, researchers are working with a harmless virus that sits in the lungs and intestines of most people. It's called a "reovirus," short for respiratory enteric orphaned virus. A Canadian company, Oncolytics Biotech, fiddles with reovirus genes to produce Reolysin, a virus that attacks a wide variety of cancers.

In a trial headed by Dr. James Markert, a neurosurgeon at the University of Alabama in Birmingham, 44 patients with brain cancer received injections of Reolysin. Preliminary results are encouraging, Markert said. "We're very optimistic that viral therapy will be one of our weapons in the fight against cancer. It could be a major piece of the puzzle."

Drs. Monica Mita and Francis Giles, at the University of Texas Health Science Center in San Antonio, are testing reovirus against bone and lung cancer.

The cancer in one of Mita's experimental patients, Kenneth Scott, has remained stable since he received an experimental injection of Reolysin a year ago.

According to Mita, the side effects of reovirus are similar to a mild cold, compared with the more serious impacts of chemotherapy.

There are multiple strategies for a virus to attack cancer, Kirn said. The virus can worm its way inside a cancer cell, multiply and kill the cell. It can act as a tiny truck or "Trojan horse," sneaking cancer-killing substances into the target cell. It can gum up the environment around a tumor so that the cancer can't spread.

Other viruses being tested as weapons against cancer include:

• The common herpes virus, the source of cold sores and genital lesions. A modified herpes virus called HSV1716 has passed preliminary tests for safety and effectiveness against brain tumors and melanoma. It's undergoing an advanced clinical trial in Great Britain.

Markert and colleagues are testing another herpes virus, known as G207, against brain cancer. "Some patients had remarkable successes," Markert said.

• Vaccinia, the first vaccine against smallpox, which Edward Jenner, an English country doctor, discovered in 1796. Also known as poxvirus, it's the basis of JX-594, an anti-cancer product developed by Jennerex in San Francisco.

In a preliminary trial, 14 end-stage liver and lung cancer patients were injected with the JX-594 virus. Half of them survived for more than eight months, well past their life expectancies of three to four months, Kirn told a meeting of the American Gene Therapy Association in Boston in May.

• A modified cold virus, called H101, which the Chinese government approved in 2005 for use against head and neck cancers.

"This is the first oncolytic virus product approved by a governmental agency for human use," Kirn reported.

China is "more open-minded about trying these novel biological therapies than people here," McCormick said. China requires only that a drug reduce the size of a cancerous tumor, not necessarily prove that it prolongs a patient's life.

"Getting approval based on patient survival is very different than just showing a shrinking of tumors," McCormick said. "Rightly, our FDA would not approve that sort of thing."

McClatchy Newspapers 2008

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