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Trial of Cancer-Fighting Virus Shows Promise
Date:8/31/2011

By Jenifer Goodwin
HealthDay Reporter

WEDNESDAY, Aug. 31 (HealthDay News) -- A new type of cancer treatment that uses a virus to infect and destroy tumor cells without harming normal cells is showing promise in early clinical trials.

The small, Phase 1 trial involved 23 patients with advanced cancers that had spread to multiple organs and who had exhausted other treatment options.

Each received an intravenous infusion of a virus called JX-594 at one of several dose levels. The virus was genetically engineered to contain an immune-stimulating gene to enhance its cancer-fighting properties, explained study co-senior author John Bell, a senior scientist at Ottawa Hospital Research Institution in Ontario, Canada.

Patients underwent biopsies eight to 10 days later. In seven of eight patients (87 percent) who received the highest two doses, researchers found evidence that the virus had not only infected the tumor cells while sparing healthy cells, but that the virus was replicating. Replication means that the virus is reproducing and infecting neighboring cancer cells, rather than just infecting tumor cells it directly came into contact with.

There was also evidence that the foreign immune-stimulating gene was expressed inside the tumor cells.

"This is a landmark observation in that it shows it's possible that a virus can find tumors, specifically grow in tumors but not in regular tissues, replicate and destroy them," Bell said.

The current trial was designed primarily to prove that it was both possible and safe to use a virus to infect tumor cells, and that the virus would then replicate. Side effects were minimal, with the main being brief and mild flu-like symptoms, researchers said.

Though larger trials are needed to determine efficacy, about 75 percent of patients in the two highest dose groups also saw a shrinking or stabilization of their tumor, while those in lower dose groups were less likely to experience this effect, according to the study.

"We didn't measure how well that specific immune-stimulating gene worked," Bell said. "But we definitely demonstrated the virus can go into the tumor, replicate only in the tumor and express a specific gene within the tumor."

The findings are published in the September issue of Nature.

One of the challenges in treating cancer is that cancer cells can spread into hard to find areas of the body, as well as in areas that can't be reached by a surgeon.

"The holy grail is a virus that could travel through the blood, find the tumors where they may be hiding, infect them and kill them," Bell explained.

Bell and his colleagues have been investigating cancer-fighting viruses for more than a decade. The virus, JX-594, is a distant relative of the smallpox virus; it's derived from a strain of vaccinia virus that has been used as a live vaccine in millions of people to vaccinate against small pox, Bell said.

In another bit of good news, the virus still infected the tumor cells even though all of the people in the study had previously been exposed to it as part of their child vaccinations, according to the study.

People in the study had several types of inoperable, advanced cancers, including lung, colorectal, melanoma, thyroid, pancreatic and ovarian. The virus can infect any type of epithelial, or surface cell, which are found throughout the digestive, reproductive, respiratory and urinary systems.

Researchers are currently planning a larger randomized clinical trial for patients with liver cancer.

William Phelps, director of preclinical and translational cancer research for the American Cancer Society, characterized the research as "preliminary, but really exciting."

"Viruses have a great capacity for finding cells in certain parts of the body. They often tend to infect only certain types of cells," Phelps said. "If we can manipulate that and take advantage of the natural capacity of the virus to spread throughout the body and to very selectively infect only certain types of cells, that could be very promising."

In this case, the virus contains "payload," or an extra gene that stimulates the immune system. "When the virus expresses that gene, it causes the immune system to kill the cell," he added. "It's very clever."

This sort of a strategy has shown lots of promise in animal models, Phelps said, but making it work in people has proven more difficult.

"The key here is they have shown you can inject virus into patients that's getting to the tumor cells, replicating and expressing this payload protein," Phelps said. "It seems to be exactly what you'd hope it would do. The next step is to go to a more defined group of cancer patients to see if it can really have anti-tumor effects."

More information

The American Cancer Society has more on cancer.

SOURCE: John Bell, Ph.D., senior scientist, Ottawa Hospital Research Institution, Ontario, Canada; William Phelps, Ph.D., director, preclinical and translational cancer research, American Cancer Society; September 2011 Nature


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