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Archive for Tuesday, April 1, 2003

Smallpox vaccine altered to fight cancer

April 1, 2003

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— The smallpox vaccine may be reborn -- as a cancer treatment.

Scientists are rigging up the vaccine to carry an extra load, genes that signal the immune system to start fighting advanced tumors.

Why use such a risky vaccine to do that job? The same super-reactive characteristics that make smallpox inoculation prone to some bad, occasionally deadly, side effects are, as the altered shots' creator puts it, "an immunologist's dream:" They may rev up an immune system that too often misses cancer.

Although still in very early stages of research, the smallpox-turned-cancer shots look promising. They're the latest in a long quest to create immune-harnessing vaccines to attack cancer.

"We're not there yet," cautions Jeffrey Schlom of the National Cancer Institute, a specialist on cancer-treating vaccines who created the smallpox vaccine-based approach. "But we're getting there."

Despite the name, most so-called cancer vaccines don't aim to prevent tumors. These are not classic inoculations like a flu shot or even regular smallpox vaccine, which teach the body to recognize and subdue an invading virus or germ.

The immune system doesn't always recognize cancer as something to attack, because tumors are made up of your own cells gone bad, not foreign germs. The hope with therapeutic cancer vaccines is to train powerful immune-system T cells to more easily spot and attack malignant cells.

More than a dozen Phase 3 studies -- the most advanced testing -- of first-generation vaccines are under way. Most involve making patients custom shots using their own tumor cells mixed with immunity-boosting chemicals. Researchers frequently see a handful of people whose cancer dramatically shrinks, even disappears, for at least a while.

But those amazing responses are rare, because cancer adapts, says NCI's Dr. Steven Rosenberg. So scientists are trying to develop more elaborate, hopefully better, vaccines.

Enter smallpox vaccine. Schlom thought it could prove a good cancer-fighting platform because it's made with live vaccinia virus, a smallpox relative that's so large that adding different genes into it is fairly easy. Also, it's highly reactive, quickly causing a distinctive, infectious pustule that clearly signals a stimulated immune system.

Schlom took a vaccinia version engineered to be milder than today's smallpox vaccine, which can occasionally cause deadly side effects. He added to it a gene that makes an antigen, or marker, called CEA that's found on many colon, pancreatic, lung and breast cancer cells. Because people become immune to vaccinia quickly, he created booster shots made with a less reactive vaccinia relative called fowlpox. And he added three immune-boosting molecules to the mix, calling it Tricom.

Injecting the altered smallpox vaccine plus boosters every few months significantly increased survival of half the patients in the first, small experiment at Georgetown University.

One patient saw her lung cancer disappear, and others who were expected to die within the year instead lived two years and counting.

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