But a new study finds that anthrax may have a not-so-sinister side: Scientists from the National Institutes of Health have developed an engineered version of the anthrax toxin that's a cancer fighter. In mice, the modified toxin killed tumors, they report in today's issue of the Proceedings of the National Academy of Sciences.
Tumor cells in humans contain high levels of a protein known as urokinase, and that protein, when expressed by the cells, is the target for the new anthrax treatment. Stephen Leppla and Thomas Bugge, both senior investigators at the National Institutes of Health, and their colleagues genetically altered the structure of the anthrax toxin so that it invades only cells that express the urokinase protein.
Why anthrax? "We knew that anthrax has to interact with a protease [such as urokinase] on the surface of the cell to kill the cell," Leppla says.
In the lab, the new treatment worked well on fibrosarcoma (a tumor of the connective tissue), melanoma and lung cancers. After one treatment, the toxin reduced tumor size by 65 percent to 92 percent, depending on the type of tumor. And two treatments eliminated 88 percent of the fibrosarcomas and 17 percent of the melanomas. The tumor cells began to die just 12 hours after the first treatment.
And the toxin did its work without damaging surrounding cells, a problem that often occurs with other cancer treatments.
The treatment is an advance in the field known as toxin fusion protein therapy, Leppla says. The approach, he says, involves "taking two different proteins, normally separate, and attaching them to be a single protein so it can have anti-disease action."
Their latest study takes the approach a step further. "Protein fusion therapy has almost exclusively targeted tumor cells by binding [the fused protein] to their surface," Leppla says. "Our innovation is, we are making the interaction dependent on the fact that the tumor cell has a specific protein [urokinase] on its surface. The toxin is sent to the tumor cell but is only activated if the specific enzyme, urokinase, is on the tumor cell."
Leppla says his team hopes the approach will bear out as a new and very specific way to kill tumor cells without causing damage to normal, surrounding cells.
Another expert in the field says the new study findings are a seminal advance. The approach adds a second requirement before the anticancer agent does its work, explains Dr. Arthur Frankel, a professor of cancer biology and medicine at Wake Forest University, Winston-Salem, N.C. Before the protein damages the tumor cell, the urokinase must be expressed.
"This is about the most sophisticated molecular biology discovery in the fusion protein area in a decade," he says.
Next, the approach must be studied in humans to see if it works.
"Realistically, if we begin human trials in three years, we would be doing great," Leppla says.
He predicts it will be eight to 10 years before the approach, if it bears out, will be generally available. "A small company in Denmark has the exclusive license to the technology and will try to carry it forward," Leppla says.
If the approach does bear out, it could help in many types of cancer, Frankel says. "Urokinase is present in many cancerous tumors," he says.