Bacteria found in soil called Clostridium novyi (C. novyi) is known to cause tissue-damaging infections. But researchers from John Hopkins Kimmel Cancer Center have developed a modified version that triggers an anti-tumor response in rats, dogs and humans. The breakthrough could complement existing methods to provide better targeted treatment of cancerous growths.
Led by associate professor of oncology, Shibin Zhou, the team first began investigating the potential of C. noyvi more than 10 years ago. The research was inspired by studies of century-old accounts detailing an immunotherapy called Coley toxins. This treatment arose from observations that some cancer patients demonstrated remission after acquiring certain bacterial infections.
The C. noyvi microbe relies on low-oxygen environments to thrive. This makes it a good candidate for the targeting of oxygen-starved cells in tumors, which can prove difficult to treat with chemotherapy and radiation. The team modified the bacteria to eliminate one of the toxin-producing genes and make it safer for therapeutic use, then observed its effects through a series of studies.
Rats with implanted brain tumors were the first to receive injections of the C. novyi-NT spores. The team found that the bacteria killed off tumor cells, but healthy cells as close as a few micrometers away were unaffected. Rats treated with C. novyi-NT lived for 33 days on average after the implantation of the tumor, while those who went untreated lived for an average of only 18.
Sixteen pet dogs with naturally occurring tumors were then injected with the C. novyi-NT. Six showed an anti-tumor response 21 days later, three of which had the tumors eradicated entirely. In the three other dogs, the longest diameter of their tumors was found to have shrunk by at least 30 percent.
In a Phase I clinical trial, a patient with an advanced soft tissue tumor in the abdomen received an injection of C. novyi-NT spores directly into a metastatic tumor in the arm, which led to a significant reduction in the size of the tumor in and around the bone. Though this was not without some side effects.
"She had a very vigorous inflammatory response and abscess formation," says Nicholas Roberts, Ph.D from the Kimmel Cancer Center. "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."
The study of the C. novyi-NT spore injections in humans is still ongoing, though the scientists are hopeful it could be combined with traditional forms of treatment such as chemotherapy, which is a mix that has already been studied in mice.
"Some of these traditional therapies are able to increase the hypoxic region in a tumor and would make the bacterial infection more potent and increase its anti-tumor efficiency,” says Verena Staedtke, a neuro-oncology fellow at John Hopkins. “C. novyi-NT is an agent that could be combined with a multitude of chemotherapy agents or radiation.”
The team's findings were published in the journal Science Translational Medicine.
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