- The Washington Times - Thursday, January 16, 2003

A new federal study says there could be life-saving medical benefits from anthrax, one of nature's deadliest bacteria.
Scientists at the National Institutes of Health (NIH) used a genetically engineered anthrax protein to shrink, and even destroy, a variety of cancers from hundreds of laboratory mice, according to a report this week in Proceedings of the National Academy of Sciences.
The anthrax used in the tests was genetically modified so that it did not activate unless it came in contact with a chemical on the surface of malignant tumors. The mice were not harmed by the bacteria because it did not adversely affect healthy cells.
Stephen Leppla and Thomas Bugge, co-authors of the study, discussed the findings on the Web site of the NIH's National Institute of Dental and Craniofacial Research (www.nidcr.nih.gov).
They explained how they converted a bioterrorism agent that killed five Americans in mail attacks in the fall into what may be a safe and effective cancer killer. They said their results were encouraging but stressed that they still have a long way to go before gene-spliced anthrax could be used to treat cancer in humans.
"We are currently testing the drug against mouse and human tumors, the latter having been implanted in mice. So far we have tested lung carcinomas, melanoma [a deadly skin cancer], and oral cancer," Mr. Bugge told NIDCR science writer Bob Cuska.
"We have seen a good effect in all three tumor types, and we will continue the testing over time in a variety of other tumor types. So, there are certainly many years of work ahead before we, or anyone who takes up this project, can test it in people," said Mr. Bugge, a researcher in NIDCR's Oral and Pharyngeal Cancer Branch.
Mr. Leppla, a scientist in NIDCR's Oral Infection and Immunity Branch, who has spent most of his career studying anthrax, agreed. "It's also important to remember that many things that look very good in cell culture or in mice turn out to have unexpected toxicities," he said.
They reported promising results in the tests, noting that one modified anthrax-protein injection reduced the size of lung tumors in the mice by an average of 65 percent and shrank soft-tissue tumors 92 percent.
After two treatments with the experimental toxin, lung tumors became 86 percent smaller, and soft-tissue tumors were 98 percent smaller. Melanoma tumors turned 85 percent smaller after one treatment and 92 percent smaller after two.
The researchers also reported that tumor cells began dying 12 hours after the treatment began. They added that many tumors including nearly 90 percent of soft mouth cancers completely disappeared after two anthrax injections.
The modified toxin seeks out a particular type of cancer cell, marked by a high level of an enzyme called urokinase, which is found on the surface of the cell.
This toxin is activated only by urokinase. In that respect, it differs greatly from the deadly toxin in natural anthrax.
The latter is activated whenever it comes in contact with furin, an enzyme in all living cells.
Scientists believe urokinase plays an important role in the spreading of cancer through the body, the two researchers said.
The modified toxin also did not harm healthy cells adjoining the tumors, because there were no urokinase enzymes on the surface of those cells, they said. If this new treatment proves effective in fighting cancer in humans, its methodology would have benefits over chemotherapy, which sometimes harms neighboring healthy cells.
Dr. Leppla said that he's certain these modified proteins cannot cause anthrax infection. "We start with a thoroughly disabled anthrax strain," he said, adding that by themselves, these proteins are "incapable of causing anthrax."
"We are simply interested in exploiting the natural properties of these proteins, in hopes of efficiently delivering a deadly toxin directly to tumor cells and killing them."
He compared the toxic proteins used in the treatment "to grenades with the pins still inside them." They "don't turn deadly," he said, "until they are cleaved on the surface of the tumor cell."


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