Modified Bacteria can Treat Tumors in Rats, Dogs and Humans
Researchers from the Johns Hopkins Kimmel Cancer Center have found a potentially new way to treat tumors that do not respond to chemotherapy or radiation. In the study, the team created a modified version of a bacterium called Clostridium novyi that was capable of creating an anti-tumor response when injected into rats, dogs and humans.
According to the researchers, the bacterium, which can be found in soil, naturally thrives in oxygen-deprived settings. Based on how the bacterium lives in nature, the researcher set out to see if it could help kill oxygen-starved cells found in tumors. The team modified the bacterium by removing the genes responsible for producing toxins, which have been linked to causing tissue-damaging infections in cattle and humans.
The bacterium spores were first tested in rats that were given brain tumors known as gliomas. In this experiment, the researchers found that the injection was able to kill tumor cells without hurting the healthy ones. The rats that were treated lived an average of 33 days after the tumor was implanted. The sick rats that were not injected with the bacterium spores lived an average of 18 days after their brain tumors were implanted.
The team then recruited 16 pet dogs that were diagnosed with tumors that had developed naturally. They modified Clostridium novyi spores were directly injected into the tumors. Within 21 days after the injection, six of the dogs had exhibited an anti-tumor response. Half of the dogs had their cancer cured. In the remaining three dogs, the longest tumor shrunk by at least 30 percent. Side effects included a bacterial infection, characterized by symptoms such as a fever and inflammation.
"One advantage of using bacteria 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 Anderson Cancer Center and the director of experimental therapeutics at the Kimmel Cancer Center's Ludwig Center for Cancer Genetics and Therapeutics.
The researchers also tested the bacterium in a Phase I clinical trial carried out at the MD Anderson Cancer Center. In this study, the researchers injected the Clostridium novyi spores directly into a metastatic tumor located on a female patient's arm. The patient had advanced soft tissue tumor in the abdomen. The injection helped reduce the tumor in and around her bones.
"She had a very vigorous inflammatory response and abscess formation," said Nicholas Roberts, Vet.M.B., Ph.D., reported in the press release. "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."
Zhou added, "Another good thing about using bacteria as a therapeutic agent is that once they're infecting the tumor, they can induce a strong immune response against tumor cells themselves. We expect that some patients will have a stronger response than others, but that's true of other therapies as well. Now, we want to know how well the patients can tolerate this kind of therapy."
The study was published in the journal, Science Translational Medicine.