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Anthrax toxins may help fight cancer

BETHESDA, Md., Jan. 13 (UPI) -- Genetically altered anthrax toxins have been used to kill cancerous tumors in animal experiments, researchers reported Monday.

This sword-to-plowshare technique "seems to have excellent effectiveness against at least three different kinds of tumors in mice," researcher Stephen Leppla, a biochemist at the National Institutes of Health in Bethesda, Md., told United Press International. "As far as we can tell and predict, it could be effective against all types of cancers."

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In mouse versions of lung cancer, melanoma and a kind of skin cancer known as fibrosarcoma, one simple treatment of the new therapy reduced tumor size by between 65 percent to 92 percent. Two doses completely eliminated 88 percent of fibrosarcomas and 17 percent of melanomas. Diseased cells began dying just 12 hours after the first treatment.

In findings reported Monday in the online Proceedings of the National Academy of Sciences, all damage apparently was restricted to the tumors, with no toxic side effects seen in normal tissues.

"It's surprising it worked as well as we hoped," Leppla said. "Ideally, we could imagine getting this into human safety trials in three to four years if everything went well. It would be another three to five years before it could be approved for use -- so five to eight years would be doing well."

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Chemotherapies against cancer for decades have been plagued by their toxic side effects. In addition, when exposed to repeated doses of the same chemotherapy, tumors often acquire drug resistance, requiring larger, more toxic doses of the drugs.

Since the 1980s, scientists have experimented with chemotherapies that use biological weapons from deadly germs such as the ricin or diptheria microbes. Unlike other chemotherapies that work by targeting DNA, which require large doses per cell for success, the germ toxins attack key proteins, requiring millions fewer molecules to kill each cell.

"Just to clarify -- this substance is a long way from the bacteria that causes anthrax infections. It's one of thousands of proteins the bacterium makes, and it's modified genetically," Leppla said. "By themselves, they are incapable of causing anthrax."

The new technique fuses a lethal anthrax toxin with another protein the germ uses to bind to specific targets. This specificity helps keep the modified toxin contained within cancer cells, reducing its danger to the patient.

The toxin's target is a chemical linked with urokinase, a protein normally found in immune cells. In humans, tumor cells usually contain high levels of urokinase, which scientists think allows cancers to digest the glue that holds cells together "so it can expand into other parts of the body," Leppla explained.

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The researchers still must determine what dosage levels or schedules would be most beneficial for treatment, "and we might yet find some unexpected toxicity," Leppla said. Also, repeated injections of proteins such as these chemicals often causes the body to generate antibodies that can inactivate the drugs.

"There's a lot of work to go," Leppla added.

Nevertheless, "here's a field that many people have been struggling and battling in, for more and more specific therapies that are less and less toxic, but we had reached a wall," said oncologist Art Frankel of Wake Forest University School of Medicine in Winston-Salem, N.C. "All of a sudden with this engineered specificity you have this added degree of safety. I've switched over my work to follow along with theirs."

Because urokinase normally is found in immune cells, Leppla added there was the remote possibility similar techniques could help fight AIDS, because HIV breeds in immune cells.

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(Reported by Charles Choi, UPI Science News, in New York)

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