Common soil bacteria injected into solid cancers in pet dogs and one human patient shrank many of the tumors, scientists reported on Wednesday.
The preliminary findings offered hope that the experimental treatment could turn out to be more effective than existing cancer therapies for some inoperable tumors such as those of the lung, breast, and pancreas, which often fail to respond to radiation and chemotherapy. Radiation requires oxygen to kill cells, but the deep interior of tumors is nearly oxygen-free.
Chemotherapy requires blood vessels to carry drugs into tumors, whose interiors generally lack such plumbing. "But these conditions make the tumors perfect for bacteria that thrive in low-oxygen environments," said oncologist Shibin Zhou of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland, a senior author of the study.
Doctors first tried using streptococcus bacteria to attack tumors 100 years ago, but that and recent attempts with salmonella proved to be toxic, ineffective, or both.
The idea nevertheless made sense, and a decade ago Hopkins scientists resurrected the approach using Clostridium novyi soil bacteria. They genetically modified the bug by removing DNA that makes a toxic protein, and decided to inject only spores, which are less likely to cause infection. They then enlisted veterinary oncologists at seven pet clinics across the United States. Sixteen dogs, from a border collie to golden retrievers and shepherds, received injections of 100 million clostridium spores.
The scientists chose dogs rather than common lab animals because their cancers are more genetically similar to humans', potentially making the results more relevant. Tumors shrank in three of the 16 dogs, and disappeared in three more, the researchers reported in Science Translational Medicine.
At M.D. Anderson Cancer Center in Houston, a patient with retroperitoneal leiomyosarcoma, an aggressive cancer of the abdomen that had spread to her liver, lungs, bones, and arm, received an injection of 10,000 spores into a metastatic tumor in her arm. She initially ran a fever and felt severe pain (a sign that her immune system was attacking the cancer) but the tumor shrank in and around her arm bone. Tumors elsewhere continued to grow.
What seems to happen, Zhou said, is that the spores release enzymes that destroy nearby tumor cells "so precisely we call it biosurgery." Also, the immune system senses the bacteria and dispatches tumor-killing cells.
BioMed Valley Discoveries, a research and development company in Kansas City, Missouri, is recruiting patients with solid tumors that have not responded to therapy for a trial assessing the safety and optimal dose of clostridium, at M.D. Anderson and other sites. "We anticipate that proceeding through Phase 1 and future later-stage trials will take many years," said BioMed's Saurabh Saha.