Injections of bacteria in tumors are promising for cancer treatment | Science

NEW YORK CITY-"Living bacteria" and "cancer treatment" do not look promising, but some microbes seem to block tumor growth when injected into tumors, according to the data presented here on September 30 in the fourth International Conference on Cancer Immunotherapy. appear to activate an immune response that also targets the tumor.There remain questions about the safety of the approach.But considering the number of patients develop resistance or do not respond to current cancer treatments, bacterial injections have generated Interest enough is part of a new clinical trial associating bacteria with established immunotherapy.

The research echoes an experience more than a hundred years old. In the 1890s, oncologist William Coley began injecting cancer patients with inoperable tumors with a mixture of killed bacteria. Coley reported the success of this approach and her "Coley toxins" were sold as cancer treatment in the United States until the 1960s. Other doctors questioned Coley's results and the treatment was been overtaken by chemotherapy and radiation therapy, which have become the norm in cancer.

Four years ago, a large team of cancer scientists suggested that bacterial injections could be a valuable way to treat cancer. They published an article in Translational medicine of sciences describing how in six of the 16 dogs with solid tumors, the masses decreased or even disappeared when they received living copies of the bacteria Clostridium novyi. As part of this work, the research team first removed a toxin-producing gene from a live bacterium. Encouraged by the dogs' behavior, the group also treated a 53-year-old woman with leiomyosarcoma, a form of cancer that begins in the smooth muscle. Her tumor also decreased, although she then sought another treatment for cancer.

This patient is now the first of many. In another clinical work conducted by medical oncologist Filip Janku at the MD Anderson Cancer Center of the University of Texas at Houston, which was part of the scientific team 4 years ago, 23 other patients with advanced sarcoma or other solid tumors ranging from breast cancer to melanoma a single injection into their tumor of 10,000 to 3 million Clostridium spores, a dormant form of the bacteria. The research team was surprised and excited about the anti-tumor effects of the bacteria. Nineteen patients, including the first woman, had their cancers stabilized, which meant that their tumors did not continue to develop after treatment. Even though the injections were local, the bacteria sometimes seemed to stabilize and reduce the growth of the tumor elsewhere in the body, as seen in the imaging, says Janku.

An inflammatory response to spores can generate essential anti-cancer immune action, speculate his colleagues. In 11 of the patients, the researchers found that the spores had sprouted, fever, pain and swelling of the injection sites, process by which the dormant bacteria resume their active reproduction.

The strategy was so new that scientists were unsure of the importance of the dose, especially because they hoped the spores would become active once in the tumor. It turned out that the number of spores injected was a key factor in safety: the two patients who received the six highest doses developed gangrene and sepsis, a potentially life-threatening reaction at the same time. infection. A third patient, also in a higher dose group, also had sepsis.

"We have not looked into the mechanism," says Janku. Non-thorny bacteria release various enzymes that can degrade tumor cells and, like any invader, send the immune system into an inflammatory state that can also target the cancerous masses. But the details remain mysterious.

Nevertheless, on the basis of stabilized tumor masses in many patients, "you know it works," says Dzana Dervovic, immunologist at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada, who is interested especially fevers followed by cancer reactions. .

The primary focus of the trial was to establish the immediate safety of bacterial injections – although it offered allusions to antitumor action, it was not designed to assess survival, or even how patients responded in the long term. Patients, who were treated between 2013 and 2017, received only one injection (with the exception of one person who requested and obtained a month later, which was not effective) then followed another treatment. To learn more, Janku opened another small trial earlier this year, with the support of two companies, to test Clostridium in combination with a "checkpoint inhibitor" drug that helps the immune system to free itself from tumors. Such medications are an increasingly popular immunotherapy strategy, one that has been rewarded today by a Nobel laureate.