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Hope and fear: Part III

The promise of viral therapies

Continued from Page 1

Once inside that cell, the viral intruder makes so many copies of itself they bust the host from the inside out and set off to find another.

Dr. Lee had centred his work on the reovirus, a bug so common it usually triggers at least one bout of diarrhea in most people by the age of 3, but it helped to spread wide interest in the viral field.

Researchers at McMaster University in Hamilton and others in Britain, for example, have homed in on the anti-cancer powers of herpes. Researchers at Duke University in North Carolina are running with a crippled poliovirus, and at Minnesota's Mayo Clinic it's a modified form of measles. University of Ottawa scientists, meanwhile, have been studying a range of microbes with an eye to tailoring them to be a tumor's worst enemy.

On a recent blustery morning at the Ottawa Regional Cancer Centre, Dr. Bell and his team crammed into his cluttered office to discuss the learning curve.

Dr. Bell, an affable, silver-haired man in black jeans, is a senior scientist with Cancer Care Ontario and a co-founder of the Canadian Oncolytic Virus Consortium, which is establishing standards in the field.

It was, for example, once thought that a virus might simply be injected into a tumour. But since cancer usually kills when it spreads, Dr. Bell said, it's clear viruses have to be given intravenously to flush the system, "if they are going to be useful."

Research suggests that 80 per cent of cancer cells have a defect that makes them susceptible to a virus. But "just as viruses have evolved ways to enter our cells," he said, "our immune system has evolved to stop them."

Figuring out how to keep the body's immune system from killing viruses that have been dispatched to kill the cancer is one of the field's key issues.

"It's been a matter of finding that balance between attenuating a virus to minimize side effects and yet not to the point where it's losing its anti-cancer punch."

Most safety trials have not even reached a maximum-tolerated viral dose in patients, he suspects, because they have involved either less virulent strains, or those genetically tweaked to be less toxic.

Dr. Bell's initial investigations focused on the Newcastle virus, a flu bug that strikes chickens. Since few patients are likely to have been exposed to the fairly obscure virus, he estimates it has "a two-week window to attack tumour cells before [a patient's] immune system gears up to destroy it."

A few years ago, Dr. Bell teamed up with a Maryland company called Provirus Inc., to run clinical trials of Newcastle virus. Thirty patients with a range of advanced cancers were enrolled in Ottawa and another 18 in Hamilton in 2001.

McMaster professor Sébastien Hotte, a medical oncologist at the Juravinski Cancer Centre, said the Phase 1 testing and follow-up was designed only to determine safe doses of the virus, but it also showed promising results in six of the 18 patients, who had all exhausted standard treatments.

Dr. Hotte, author of the report that is soon to be published, said the virus was delivered by IV twice a week for three weeks. If the treatment was well tolerated, the infusions continued over several months.

The first dose prompted "flu-like" symptoms, but they disappeared with subsequent doses as the body acclimatized to the treatment.

"We were quite happy," Dr. Hotte said, "some patients had signs of disease regression."

The most dramatic example involved a woman in her 40s with end-stage cervical cancer who received the viral infusions for nine months. Some months after treatment ended, surgeons operating to remove a benign growth on her bladder discovered her cancer had disappeared. More than three years later, Dr. Hotte said, the woman is still alive.

He said the therapy is "not ready for prime time," but noted that larger trials of the virus in patients with cervical and colorectal cancers are to begin in Hamilton next year.

"Given that we have a lot of people who are drug averse, [patients] find this approach very attractive. It's not a chemical, it's not chemotherapy, and that," he said, "is appealing to them."

It was Calgary virologist Dr. Lee, along with his postdoctoral student Jim Strong and his graduate student Matt Coffey, who first paid Dr. Thompson a visit in 1998.

Since then, the garden-variety reovirus that led to their breakthrough has become the cornerstone of Oncolytics.

So far, 100 patients have received treatment with Reolysin in six preliminary safety trials, three of them in Alberta. The company has also been testing it on cancer patients in England and recently received approval to expand the trials.

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