Clostridium novyi, a type of bacteria that lurks in soil and feces, can cause a range of mild illnesses when it finds an oxygen-free area to grow and multiply. The area at the center of a cancerous tumor can offer the bacteria just the right environment, spurring research into whether C. novyi could be used to fight cancer.
Johns Hopkins researchers genetically modified the bacteria to make it less toxic. Then they injected it directly into tumors growing inside live patients — 16 canine and one human — who were treated at Houston’s MD Anderson Cancer Center. The researchers reported promising results in a paper recently published in Science Translational Medicine.
The human patient’s tumor that was treated with bacteria shrank, while other tumors in the patient's body continued to grow.
Three of the dogs were cured of cancer completely, and three others saw their tumors shrink by at least 30 percent. In some of the other cases, the tumors turned out not to have oxygen-free regions for the bacteria to infect.
The injected bacteria sought out and infected anaerobic cells (which do not require oxygen) deep inside the tumors. Once inside those cells, the bacteria made enzymes that damaged cell walls and proteins. And because the body recognized the bacteria as an intruder, its presence jumpstarted the body’s own cancer-fighting immune response.
Who Let the Dogs In?
The study focused on pet dogs, with their owners’ consent, who had few proven treatment options available to them. Their cancers, which developed naturally inside a living animal, offered better study models than tumors grown in petri dishes and implanted into mice.
“In the real human population, everyone is different; every tumor is different,” said study author Dr. Shibin Zhou.
But in conventional mouse research, “you take mice and you implant tumors in them, and all the tumors will be identical and all the mice are identical because they’re identical twins.” That uniformity skews the study results, Zhou said.
Fine-Tuning Techniques from the Past
Zhou and several colleagues began exploring C. novyi's cancer-fighting potential 10 years ago after reading the 100-year-old accounts of New York doctor William Coley, who noticed that cancer patients sometimes went into remission after they contracted a serious bacterial infection.
Coley later tried isolating bacteria and injecting it into cancer patients. But besides toxicity problems, Coley’s timing was unlucky.
“That’s when chemotherapy and radiation therapy were developed, so people started to forget about the bacterial therapy,” Zhou said.
But treatment with the modified C. novyi bacteria could complement chemotherapy because some drugs work by cutting off the tumor’s blood supply — and, with it, oxygen.
Any cancer that results in large tumors could play host to the bacterial infection. Although there’s no standard diagnostic test to determine which tumors have low-oxygen areas in them, C. novyi can’t get a foothold anywhere else, so the risk to patients appears low.
"The bacteria are exquisitely sensitive to oxygen, so they can only replicate in tumors, not in normal cells where there’s oxygen," said Zhou.
Indeed, the paper's authors describe the treatment as a kind of “biosurgery.”
“It’s quite precise, almost like a surgical procedure,” said Zhou.