Testing Underway on Cancer-Killing Bacteria
A bacterium that in its natural state can cause tissue-damaging infection in cattle and sheep, as well as humans, has been modified by researchers to attack cancerous animal and human cells.
New research out of the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, and included in a paper published online Aug. 13 in the journal Science Translational Medicine, shows a manipulated modified version of the Clostridium novyi (C. novyi-NT) bacterium can produce "a strong and precisely targeted anti-tumor response in rats, dogs and now humans," according to a cancer center news release.
The C. novyi microbe thrives only in oxygen-poor environments, which makes it capable of being used to target and eradicate oxygen-starved cells in tumors that are otherwise difficult to treat with chemotherapy and radiation.
The Johns Hopkins team explained it removed one of the bacteria's toxin-producing genes, leaving it safer for therapeutic use.
The team tested direct injections of C. novyi-NT spores into the tumors of 16 pet dogs that were being treated for naturally occurring growths.
Six of the dogs had an anti-tumor response 21 days after their first treatment, while three of the six showed complete eradication of their tumors.
As well, the length of the longest measured tumor diameter shrank by at least 30 percent in the three other dogs.
Most of the dogs experienced side effects typical of a bacterial infection, such as fever and tumor abscesses and inflammation, the study said.
"One advantage of using bacteria to treat cancer is that you can modify these bacteria relatively easily, to equip them with other therapeutic agents, or make them less toxic as we have done here," said Shibin Zhou, associate professor of oncology at the cancer center and director of experimental therapeutics at the Kimmel Cancer Center's Ludwig Center for Cancer Genetics and Therapeutics.
He and colleagues at Johns Hopkins began exploring C. novyi's cancer-fighting potential more than a decade ago after studying hundred-year old accounts of an early immunotherapy called Coley toxins, which grew out of the observation that some cancer patients who contracted serious bacterial infections showed cancer remission.
Verena Staedtke, a Johns Hopkins neuro-oncology fellow, first tested the spore injection in rats with implanted brain tumors called gliomas. Microscopic evaluation of the tumors showed that the treatment killed tumor cells but spared healthy cells just a few micrometers away. The treatment also prolonged the rats' survival, with treated rats surviving an average of 33 days after the tumor was implanted, compared with an average of 18 days in rats that did not receive the spore injection.
Then researchers extended their injection tests to dogs - the tumors of which share many genetic similarities with human tumors; additionally, dogs are also treated with many of the same cancer drugs as humans and respond similarly.
Zhou said study of the C. novyi-NT spore injection in humans is ongoing, but the final results of that series of treatments are not yet available.
"We expect that some patients will have a stronger response than others, but that's true of other therapies as well," Zhou said. "Now, we want to know how well the patients can tolerate this kind of therapy."
It may eventually be possible to combine traditional treatments like chemotherapy with the C. novyi-NT therapy, said Zhou, who added researchers have already studied such treatment combinations in mice.
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