Researchers looking for a novel strategy to fight pancreatic cancer say they have found that radioactive bacteria can attack and kill diseased cells without harming healthy tissue.
With a five-year survival rate of only 4 percent, pancreatic cancer is one of the deadliest forms of the disease. The National Cancer Institute predicts more than 45,000 new cases of pancreatic cancer will be diagnosed and nearly 38,500 people will die from it this year. The disease is often difficult to fight because it is hard to detect in its early stages., The cancer has typically already spread or metastasized by the time noticeable symptoms appear, and there are currently no effective cures for its advanced form.
Scientists at the Albert Einstein College of Medicine in New York City were investigating the bacterium Listeria monocytogenes as a potential vehicle to deliver treatments for the cancer. Wild versions of the microbe are responsible for causing a dangerous form of food poisoning, but the researchers were experimenting with a weakened strain of the organism. The idea was to use a genetically modified version of the germ to carry molecules normally seen on tumors around the body so the immune system could recognize cancerous cells as threats — the biological equivalent of passing around wanted posters to police officers.
Unexpectedly, they discovered that even when weakened, Listeria could infect cancer cells.
"We were very surprised to see the Listeria infecting the tumors,” says Claudia Gravekamp, an associate microbiology and immunology professor who led the research.
Fighting fire with fire
The bacterium was able to infect cancer cells because tumors pump out molecules known as cytokines that suppress immune cells. Normally cytokines help protect tumors by preventing the immune system from attacking compromised cells, but cytokines have no effect on Listeria, so the germs were able to bypass the defensive mechanism.
To make Listeria dangerous to cancers without also making the bacterium more dangerous to healthy cells, the scientists decided to attach the radioactive isotope rhenium-188 onto the microbe. This radioactive material accumulates in tumors as the bacteria infect them, killing the cancers with radiation over time. Rhenium-188 emits beta particles, a form of radiation that is highly effective against cancer. However, in healthy tissue, immune cells quickly destroy the weakened germs and clear them from the body before they have time to seriously damage healthy cells with radiation.
"The Listeria is less harmful to patients than chemotherapy,” Gravekamp says.
In experiments, the scientists injected the radioactive bacteria into mice with pancreatic cancer once a day every day for one week, followed by one week of rest and single injections on four additional days. The bacteria grew rapidly in tumors and not at all in healthy tissues, resulting in a 90 percent reduction in the number of metastatic tumor cells and a 64 percent reduction in the primary pancreatic tumors that were the source of the metastasis compared with untreated mice. Neither the radiation nor the bacteria were detectable one week after treatment, and the mice apparently experienced no significant ill effects.
"We were very excited because it is very difficult to treat pancreatic cancer," says researcher Ekaterina Dadachova, a radioimmunotherapy specialist at Albert Einstein College of Medicine. "We were able to eliminate metastases in this mouse model of pancreatic cancer, and we hope that this will be also possible in humans."
The research team’s goal now is to clear 100 percent of the metastatic tumors, since any cancer cell can potentially form new tumors. The scientists plan on refining their strategy by tinkering with the injection schedule, using higher doses of radiation or loading the bacteria with extra anticancer agents.
The scientists detailed their findings online April 22 in the Proceedings of the National Academy of Sciences and the school has filed a patent application covering their innovation.
Top Image: Tumor cells infected with radioactive Listeria (red). Photo courtesy Dinesh Chandra.