Anthrax shows promise as cancer killer

Genetically altered agent reduces tumors, NIH says


WASHINGTON - Anthrax, the biological agent that killed five people in 2001 and frightened millions more, may be an effective cancer killer, according to new research from the National Institutes of Health.

Genetically engineered anthrax protein - designed to activate only on contact with a chemical on the surface of malignant tumors - greatly reduced and even eradicated cancers in tests on hundreds of mice, according to a study published yesterday in the Proceedings of the National Academy of Sciences. As a result of the genetic engineering, the anthrax did not poison the mice.

Three main types of tumors - soft-tissue fibrosarcoma, skin melanoma and lung carcinoma - responded to the anthrax protein, which is a key component of anthrax bacteria, said Dr. Stephen Leppla, an NIH scientist and co-author of the study. In theory, the new toxin should work on all or almost all forms of cancer, he said.

In trials on mice, a single customized anthrax-protein injection reduced the size of lung tumors by an average of 65 percent, Leppla reported, and soft- tissue tumors by 92 percent.

After two treatments, tumors were 86 percent to 98 percent smaller, respectively. Melanomas were 85 percent smaller after one treatment, 92 percent after two.

After two anthrax injections, many tumors - including 88 percent of soft-tissue fibrosarcomas in the mouth - "were completely eradicated," researchers reported. Tumor cells began dying 12 hours after anthrax treatment began.

The results suggest that there's a good use for one of nature's deadliest bacteria, said Dr. Thomas Bugge, an NIH scientist and study co-author. "We are at a very early stage, and it will take years before we are ready to try it in humans," he added. "I'm excited, but also cautious about the idea."

For more than 20 years, cancer researchers have been investigating some of the same toxins that terrorists consider, including diphtheria and the nerve agent ricin. They produced nasty and sometimes fatal side effects, however. A diphtheria-derived anti-cancer agent is the only candidate to have gained federal approval and is used as a cancer drug of last resort.

In addition to yielding an effective new cancer toxin, the anthrax finding "revolutionizes the field" by providing a new technique to keep the toxins from attacking healthy, noncancer cells, said Dr. Arthur Frankel, a leading cancer toxin biologist at Wake Forest University in Winston-Salem, N.C.

"It's the most important breakthrough in our field in the last 20 years," said Frankel, who was not involved in the study.

In effect, the engineered anthrax can tell the difference between cancer cells and healthy ones.

Normally, the deadly toxin in anthrax bacteria is activated when it finds furin, an enzyme in all living cells. Until then, it is like "grenades with the pins still inside them," Leppla said.

Leppla and Bugge altered chemicals in the anthrax protein so it would not be activated by furin, but only by an enzyme called urokinase, which is found on the outside of cancer cells.

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