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Viral therapy delivered intravenously goes to cancer tumour sites: study

From Canadian Press DataFile (August 31, 2011)

By Anne-Marie Tobin

TORONTO -- A cancer-fighting virus can be delivered intravenously and appears to target solid tumours without harming the healthy tissue that's nearby, researchers say.

A preliminary trial involving 23 patients with advanced cancers who were given infusions of the JX-594 virus was designed in part to establish safe dosages and see if the viral therapy would indeed reach the tumours.

The researchers in Ottawa, the United States and South Korea were encouraged by their findings, published this week in the journal Nature.

"No one's ever been able to show before that they could deliver (virus) intravenously and see tumour targeting, so other people have tried ... and were unsuccessful," co-author Dr. John Bell of the Ottawa Hospital Research Institute said Wednesday.

"This is the first time we've been able to show we can give the virus intravenously, it definitely gets to the tumour sites, it spreads throughout them quite nicely, and begins to destroy the tumour. That really is the first."

The scientists increased the dosage -- for a total of five levels -- with successive patients. Seven of the eight patients in the two highest dose groups had evidence of viral replication in their tumour but not in the normal tissue, the study found, and six of the eight patients had a shrinking or stabilization of their tumours.

The most common side-effect was mild to moderate flu-like symptoms that lasted less than a day, Bell said, adding that the side-effects of other kinds of cancer treatment such as chemotherapy and radiation can be "quite difficult."

In this case, patients had run out of treatment options and Bell said they "very bravely" volunteered to take part in the clinical trial and receive a single infusion, which took about an hour and involved an overnight stay.

Biopsies were obtained eight to 10 days after the infusion, and tissue was examined under a microscope.

The JX-594 virus was designed by the company Jennerex Inc., co-founded by Bell and Dr. David Kim of San Francisco, from a strain used as a vaccine against smallpox.

"This virus is not smallpox, but it looks enough like it to the immune system that when you get treated with it you are prevented from getting a smallpox infection. So this virus has been used for 200 years to treat people, or vaccinate people against smallpox. It's very safe," Bell explained.

"And then it's just been taken and re-engineered to be more selective so it only grows in cancers and not normal tissues."

Michael Wosnick, vice-president of research at the Canadian Cancer Society, said cancer-fighting viruses have been injected directly into tumours in humans before, but this trial indicates an intravenous viral therapy can find tumours and infect them.

He described it as exciting development, but said it is a first step and larger clinical trials are required to see what the overall impact on patients would be.

"This allows you potentially to think about a systemic application through the whole body where the virus is now going to all those distant cancer sites, and all those distant cells and actually seeking out, and hopefully in the end destroying them. So this is a much more powerful approach than being able to inject in a tumour by tumour basis."

More research is underway.

"We're now starting a larger trial which will involve 120 patients and will give them multiple treatments, and hope to show our virus is better than the current therapies that are out there," Bell said.

The initial study also showed that it's possible to add non-viral genes that might have value -- sort of "extra payloads into the virus," he said.

"You can now deliver it through this virus infection, for example, put in a gene that might help you image the tumour, so select the image."

The research was supported by the Terry Fox Foundation, the Canadian Institutes of Health Research, the Ontario Institute for Cancer Research, the Ottawa Hospital Foundation, the Canada Foundation for Innovation, the Natural Sciences and Engineering Research Council of Canada and the Republic of Korea.


Posted: September 2011