In the 1890s, cancer researcher William Coley noticed that some patients who developed postsurgical infections went into remission. Now scientists have shown that injections of a weakened bacterium — Clostridium novyi — can shrink tumors in rats and pet dogs:
The advantage of using Clostridium novyi is that it thrives only in oxygen-poor environments, such as those prevailing deep within tumors. These troublesome spots lack the blood and oxygen needed for traditional therapies to work. But where chemotherapy and radiation struggle to have an effect, hypoxia-tolerant microbes may mount an infection and induce a strong immune response. Even better, the microbes may stop when they reach healthy tissue.
In their study, the researchers introduced several innovations: They removed one of the Clostridium novyi bacterium’s toxin-producing genes to make C. novyi-NT, which is safer for therapeutic use. They elected to inject bacterial spores directly into tumors rather than rely on the intravenous route. (In earlier studies, few bacterial spores that had been injected into experimental animals actually reached tumors.) Finally, they expanded their investigation beyond rats.
“It is well known that experimental models often do not reliably predict the responses of human patients to therapeutic agents,” wrote the authors. “We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations.”
The researchers tested direct-tumor injection of the C. noyvi-NT spores in 16 pet dogs that were being treated for naturally occurring tumors. Six of the dogs had an antitumor response 21 days after their first treatment. Three of the six showed complete eradication of their tumors, and the length of the longest diameter of the tumor shrunk by at least 30% in the three other dogs. Most of the dogs experienced side effects typical of a bacterial infection, such as fever and tumor abscesses and inflammation.
“On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores,” the researchers continued. “This treatment reduced the tumor within and surrounding the bone.”
Studies in other patients are currently underway at multiple sites to test the safety and efficacy of this new approach.