Injected bacteria shrink tumors in rats, dogs and humans

A modified version of the (C. novyi-NT) bacterium can produce a strong and precisely targeted anti-tumor response in , and now , according to a new report from Kimmel Center researchers.

In its natural form, C. novyi is found in the soil and, in certain cases, can cause tissue-damaging infection in cattle, sheep and humans. The microbe thrives only in oxygen-poor environments, which makes it a targeted means of destroying oxygen-starved cells in that are difficult to treat with chemotherapy and radiation. The Johns Hopkins team removed one of the ’s toxin-producing genes to make it safer for therapeutic use.

For the study, the researchers tested direct-tumor injection of the C. novyi-NT spores in 16 pet dogs that were being treated for naturally occurring . Six of the dogs had an anti-tumor response 21 days after their first treatment. Three of the six showed complete eradication of their tumors, and the length of the longest diameter of the tumor shrunk by at least 30 percent in the three other dogs.

Most of the dogs experienced side effects typical of a , such as fever and tumor abscesses and inflammation, according to a report on the work published online Aug. 13 in Science Translational Medicine.

In a Phase I clinical trial of C. novyi-NT spores conducted at , a patient with an advanced soft tissue tumor in the abdomen received the spore injection directly into a in her arm. The treatment significantly reduced the tumor in and around the bone. “She had a very vigorous inflammatory response and abscess formation,” according to Nicholas Roberts, Vet.M.B., Ph.D. “But at the moment, we haven’t treated enough people to be sure if the spectrum of responses that we see in dogs will truly recapitulate what we see in people.”

“One advantage of using 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, M.D., Ph.D., associate professor of oncology at the Cancer Center. Zhou is also the 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.

The researchers focused on soft tissue because “these tumors are often locally advanced, and they have spread into normal tissue,” said Roberts, a Ludwig Center and Department of Pathology researcher. The cannot germinate in normal tissues and will only attack the oxygen-starved or hypoxic cells in the tumor and spare healthy

… Continue reading here.
Dogs News — Sciencedaily

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