Injecting tumors with bacteria may sound an odd way to tackle cancer, but the idea has actually been around for some time. Doctors first observed that bacterial infections can reduce or even eliminate tumors some 200 years ago. In the 1890s, a surgeon successfully treated thousands of cancer patients by injecting them with dead Streptococcus. The idea largely lost interest, but a few groups have experimented with the technique in recent years. Unfortunately, however, human trials previously yielded disappointing results.
Undeterred by this, a team of Johns Hopkins researchers have been pursuing the idea for over a decade. Now, in a recently published study using a different bacterial species to previous studies, they have demonstrated that this form of therapy may actually work. Studies in rodents, dogs and even a human have all found that this treatment can elicit a strong, specific antitumor response. The work has been published in Science Translational Medicine.
For their study, researchers used a soil bacterium called Clostridium novyi. This species is anaerobic meaning that it thrives in an absence of oxygen. This characteristic makes it an ideal candidate for cancer therapy because many cells in tumors are oxygen-starved. C. noyvi can cause infections in certain animals and humans, so the team removed its toxin-producing genes to make it safer.
The team began by injecting bacterial spores directly into the tumors of rats with a certain type of brain cancer. They found that the treatment elicited a precise, localized antitumor response, sparing healthy tissue just a few centimeters away from the tumor. Furthermore, survival rates of the animals were improved.
What happens in rodent models does not necessarily reflect what may happen in humans, however, so the researchers turned to dogs. This is because naturally occurring canine tumors are more representative of human tumors than rodent models of cancer since they can arise spontaneously and also share certain genetic similarities.
Once again, the researchers injected the modified bacterial spores into the tumors of 16 companion dogs and observed the responses. They found that the treatment was well-tolerated, although they demonstrated minor symptoms associated with bacterial infections such as fever and inflammation. The tumors were found to reduce in size in 6 of the dogs and 3 were completely eradicated of cancer.
Taking this one step further, the researchers initiated a Phase 1 clinical trial which is ongoing. One patient with advanced soft tissue tumor was injected just 1% of the dose the dogs received into a tumor in her arm. The tumor significantly shrank, but unfortunately she later died from her other metastasized tumors.
The researchers hypothesize that the therapy works because the proliferating bacteria release enzymes that destroy the cancerous cells. Furthermore, the bacteria also seem to induce a strong immune response against the tumor cells. The treatment is also very specific because the bacteria only grow in oxygen-starved tumor cells, leaving surrounding tissue unscathed. However, the localized nature of the treatment is a double-edged sword because it means it may not be useful for patients with metastases.
Of course, the researchers need to prove that the therapy works in more people before we can get too excited, but human trials are currently ongoing. The team believes the therapy may be particularly effective if combined with other treatments such as chemotherapy or radiotherapy.
[Via Science, Science Translational Medicine and Johns Hopkins School of Medicine]
