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Dog Study Suggests Bacteria as Cancer Fighter
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A modified version of Clostridium novyi bacteria, when injected into solid soft tissue tumors, will eat away at the cancerous cells without harming surrounding healthy tissue, researchers report Aug. 13 in the latest Science Translational Medicine.
Researchers injected C. novyi spores into 16 pet dogs being treated for naturally occurring tumors. The bacteria caused an anti-tumor response in six of the dogs within three weeks, researchers report.
The bacteria caused complete eradication of the tumor in three of the six dogs, while the other three showed tumor shrinkage of at least 30 percent.
The C. novyi bacteria also worked well in rats implanted with brain tumor cells.
"When we treated those tumors, we found that C. novyi was able to germinate inside the tumor while sparing the normal brain tissue," said co-author Dr. Verena Staedtke, a fellow at the Johns Hopkins Kimmel Cancer Center in Baltimore.
The treatment killed tumor cells but spared healthy cells just a few micrometers away. It also prolonged the rats' survival, with treated rodents 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 bacteria.
Based on these findings, researchers have begun phase I human trials using the bacteria at multiple sites across the United States.
In one example, a patient at MD Anderson Cancer Center in Houston received a spore injection directly into an advanced-stage tumor in her shoulder, and experienced significant shrinkage of the tumor in and around the bone, the researchers reported.
"Dog tumors resemble human tumors in many ways," said study lead author Nicholas Roberts, also a fellow at the Kimmel Cancer Center. "They're treated with many of the same drugs as humans, and they experience the same toxicities. That was the rationale for treating pet dogs in this study."
The idea of using bacteria to fight cancer has been around for more than a century, when early cancer researchers found that the presence of certain bacteria appeared to limit tumor development, said senior author Dr. Shibin Zhou, director of experimental therapeutics at the Kimmel Cancer Center's Ludwig Center for Cancer Genetics and Therapeutics.
Bacteria that are anaerobic -- thriving in oxygen-depleted environments -- can serve as an effective means of destroying oxygen-starved cells deep inside solid tumors.Chemotherapy and radiation therapy are less effective against these oxygen-starved cancer cells, Zhou said.
Up until now, the problem has been that most bacteria effective against cancer also can do great harm to patients. "Bacteria is very toxic, and those toxins are left behind and can cause problems for the patient," said Greg Adams, director of biological research and therapeutics for Fox Chase Cancer Center in Philadelphia.
The researchers created a safer version of the C. novyi bacteria by removing a toxin-producing gene.
"Those side effects are typically very well-tolerated and managed in this study," Roberts said.
And because C. novyi is anaerobic, it didn't appear able to spread into the oxygen-rich healthy tissues outside the tumor, researchers found.
If these results pan out in humans -- and scientists note that animal research often fails to provide similar results in humans -- bacterial treatment of tumors could be a promising new cancer therapy, Adams said. But researchers will probably need to show that the bacterial infection also triggers the immune system to attack the cancer, he said.
"For this to reach the big-time, you need to be able to trigger the immune response with this treatment," he said. Chemotherapy and radiation therapy are effective partly because they draw the immune system into the fight, he noted.
However, Adams said he doesn't think the therapy would be as useful if a person has multiple tumors, or has tumors in locations where an infection could do more harm than good.
"The thought of building an abscess in the brain is scary for me," he said. "I'm not sure how you would manage that."
SOURCES: Verena Staedtke, M.D., Ph.D., fellow, Johns Hopkins Kimmel Cancer Center, Balitmore, Md.; Nicholas Roberts, Vet.M.B., Ph.D., fellow, Johns Hopkins Kimmel Cancer Center; Shibin Zhou, M.D., Ph.D., director, experimental therapeutics, Kimmel Cancer Center's Ludwig Center for Cancer Genetics and Therapeutics; Greg Adams, Ph.D., director, Biological Research and Therapeutics, Fox Chase Cancer Center, Philadelphia, Pa.; Aug. 13, 2014, Science Translational Medicine
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