• 4/8/2002
  • Washington DC
  • Reuters

A genetically engineered virus designed to home in on and kill cancer cells may be safe to test in patients whose cancer has spread, researchers said on Monday.

The latest in a series of experiments using Onyx-015, a cold virus altered so that it infects and kills only cancer cells and leaves healthy cells alone, produced positive results on liver cancer, the researchers said. Richmond, California-based Onyx Pharmaceuticals Inc. has been testing the virus for several years, using a variety of novel approaches such as putting it into a mouthwash to treat oral cancer and injecting it into tumors.

In the latest experiment they infused the virus into the livers of patients whose cancers had spread there. “Rather than injecting it directly into the tumor using a syringe and needle, where it might not get distributed evenly, we injected it into the artery, so that the flow of blood carries it throughout the liver,” Dr. Daniel Sze of Stanford University Medical Center in California, who helped lead the study, said in a telephone interview.

The phase I study was meant only to test the safety of the approach, and Sze told a meeting in Baltimore of the Society of Cardiovascular and Interventional Radiology it seemed safe. They tested 35 patients whose gastrointestinal cancer, mostly colon cancer, had spread into the liver. None could be cured by surgery and chemotherapy had stopped working for them, so they were dying of their cancer. Not only was the treatment safe, Sze told the meeting, but it seemed to help fight the tumors. Such patients usually live only six to eight months but the median survival time of this group was just over a year. CT scans showed the livers swelled at first, perhaps a sign of inflammation from the treatment.

TUMORS SHRANK AFTER TREATMENT

“The tumors shrank somewhat, but more impressive was that blood tests showed that abnormal proteins being secreted by the tumors either decreased significantly, or became completely undetectable,” Sze said. “That suggests the tumors, although still visible on the CT scan, are dying or dead.”

The researchers were also scheduled to report on their findings to a meeting in San Francisco of the American Association for Cancer Research. Colon cancer kills 50,000 people every year in the United States, making it one of the deadliest cancers after lung, breast and prostate cancer. It often spreads to the liver, and is very difficult to treat at that stage.

Sze said Onyx-015 might offer an effective way to treat the cancer without the side-effects of chemotherapy. “Standard chemotherapy kills some healthy cells along with the cancer. This engineered adenovirus is designed to kill only the cancer and not to harm healthy cells,” he said. The adenovirus his team used is a relative of the common cold virus. When it attacks cells it uses a protein called p53, which happens to help repair the kind of damage that leads to cancer.

About 60 percent of cancer cells have mutated p53 genes. Researchers changed the adenovirus so that it could not make use of p53 and therefore should not be able to invade healthy cells, but could attack cancer cells with faulty p53. Sze said his team realized that infusing a virus into the liver could be dangerous. Such a treatment killed 18-year-old Jesse Gelsinger in 1999 in a gene therapy experiment. Sze said the cancer experiment took this into account. “The maximum dose (used in the Gelsinger case) was something like 25 times as high as our maximum dose,” he said.

“That is the Jesse Gelsinger legacy — you can’t indiscriminately keep going up. Also, even though our patients had tumors, their liver function was normal. We were certainly aware that if we gave too much stress on the livers they could go into liver failure.”

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