NEW YORK CITY—“Live bacteria” and “cancer treatment” may not sound like a promising match, but certain microbes seem able to stall tumor growth when injected into the tumors, according to data presented here on 30 September at the Fourth International Cancer Immunotherapy Conference. The injections appear to activate an immune response that also targets the tumor. There are still questions about the safety of the approach. But given how many patients develop resistance or don’t respond to current cancer treatments, bacterial injections have generated enough interest that they’re part of a new clinical trial combining bacteria with an established immune therapy.
The research carries echoes of a more-than-a-century-old experiment. In the 1890s, oncologist William Coley began to inject cancer patients who had inoperable tumors with a mixture of killed bacteria. Coley reported success with the approach and “Coley’s toxins” were sold as a cancer therapy in the United States even into the 1960s. But other doctors questioned Coley’s results, and the treatment was overtaken by chemotherapy and radiation, which became standard in cancer.
Four years ago, a large team of cancer scientists suggested bacterial injections might be a valid way to treat cancer after all. They published a paper in Science Translational Medicine describing how in six out of 16 dogs with solid tumors, the masses shrank or even disappeared when injected with live copies of the bacterium Clostridium novyi. In that work, the research team first removed a toxin-producing gene from the live bacteria. Encouraged by how the dogs fared, the group also treated a 53-year-old woman with leiomyosarcoma, a form of cancer that begins in smooth muscles. Her tumor shrank as well, though she later sought other treatment for the cancer.
That patient is now the first of many. In additional clinical work led by medical oncologist Filip Janku at the University of Texas MD Anderson Cancer Center in Houston, who was part of the scientific team 4 years earlier, 23 more patients with advanced sarcoma or other solid tumors ranging from breast cancer to melanoma got a single injection into their tumor of anywhere from 10,000 to 3 million Clostridium spores, a dormant form of the bacteria. The research team was surprised and excited by the bacteria’s antitumor effects. Nineteen patients, including that first woman, saw their cancers stabilize, which meant their tumors didn’t continue to grow after treatment. Even though the injections were local, the bacteria also seemed to sometimes stabilize and reduce tumor growth elsewhere in the body as seen on imaging, Janku says.
An inflammatory response to spores may generate the key anticancer immune action, he and his colleagues speculate. In 11 of the patients, the researchers saw evidence—fever, pain, and swelling at the injection sites—that the spores had germinated, the process by which the dormant bacteria resume active reproduction.
The strategy was so new that the scientists weren’t sure the dose would matter, especially because they hoped the spores would become active once inside the tumor. It turned out that how many spores were injected was a key safety consideration: The two patients who received the highest of six doses developed gangrene and sepsis, a life-threatening response to infection. A third patient, also in a higher dose group, got sepsis, too.
“We haven’t done a deep dive into the mechanism,” Janku says. The nonspore bacteria release various enzymes that can break down tumor cells, and just like any invader, they send the immune system into an inflammatory state that may target cancer masses as well. But the details remain mysterious.
Still, based on the stabilized tumor masses in so many patients, “you know it’s working,” says Dzana Dervovic, an immunologist at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada, who is especially interested in the fevers that tracked with cancer responses.
The trial was primarily meant to establish the immediate safety of the bacterial injections—though it offers hints of antitumor action it wasn’t designed to assess survival, or even how patients fared long-term. The patients, who were treated between 2013 and 2017, received just one injection (with the exception of one person who requested and got a second months later, which was not effective), and then went on to other treatments. To learn more, Janku opened another small trial earlier this year, with support from two companies, to test Clostridium in combination with a “checkpoint inhibitor” drug that helps unleash the immune system against tumors. Such drugs are an increasingly popular immunotherapy strategy, one that was today recognized with a Nobel Prize.