Scientists at two US universities successfully eradicated cancer with metastases in mice and dogs

A recent laboratory study opened a new hope that certain types of cancer will be cured, by eradicating metastases in mice and dogs, through the application of low doses of radiation which activate the immune system to “kill” tumors.

The research is being carried out by a team of scientists from medical schools at the University of Pittsburgh and the University of Wisconsin-Madison in the United States, which published the work in Scientific translational medicine.

The authors “combined TRT (targeted radionuclide therapy) with external beam radiation therapy to increase the response to ICI (immune checkpoint inhibitors) in mice with multiple tumors and confirmed the safety of TRT in two canine companions with cancer “, they said in the publication.

“About half of the mice with tumors resistant to IBI demonstrated a complete response to TRT, and the combination of TRT with IBI reduced metastasis,” they added.

“We are delighted: with such low doses of radiation, we weren’t expecting the response to be so positive “, said one of the study’s lead authors, Ravi Patel, assistant professor at the University of Pittsburgh and radiation oncologist at the Hillman Cancer Center at the same institution.

The usual thing is that professionals “in clinical trials we tend to go with the maximum tolerable dose, with the idea that radiation kills cancer and the more we give the better. But in this study, our concept is different: we are not trying to destroy the tumor with radiation. We are trying to activate the immune system so that it kills cancer, ”he said.

As a result of the tests, according to the scientific team’s publication, “about half of the mice with tumors resistant to ICI (immune checkpoint inhibitors) demonstrated a complete response to TRT (targeted radionuclide therapy), ICI reduces metastases ”. Although they are optimistic about the outcome, “more studies are needed to assess TRT and IBI in humans,” they said.

Cancer immunotherapies have revolutionized cancer treatments, experts believe, because they allow patients’ immune systems to fight tumors. But some people are resistant to immunotherapy and others have tumors classified as “immunologically cold” because they elude or suppress the patient’s immune response to their cancer.

For these types of patients, doctors are already applying external beam radiation therapy, known by its acronym EBRT, in which the patient is placed in a machine that directs the radiation directly to the tumor and, in many cases, manages to convert these “colds”. “or resistant tumors,” hot “so that immunotherapies are more effective.

But EBRT therapies are not indicated for patients with metastases, that is, those whose cancer has spread to other parts of the body. Thus, EBRT does not work in the presence of distant tumors as this could cause the patient not to tolerate as much radiation. Here, doctors sometimes assess the correct use of targeted radiation therapy.

The team led by Patel and his colleague Zachary Morris, associate professor of human oncology in the faculty of medicine and public health at the University of Wisconsin, also senior author, designed a study to administer variable doses of targeted radiation therapy to mice with immunologically cold metastatic cancers in conjunction with immunotherapy.

“Since the radiation from a targeted radionuclide therapy, if administered at too high a dose or at the wrong time, could kill or damage the immune cells infiltrated into the tumor we ultimately want to destroy these tumors,” it was essential to design these studies with precise knowledge of the dose of radiotherapy and the time during which it would be delivered to the tumor ”, Morris explains.

Patel and Morris worked with a group of medical physicists led by the Bryan Bednarz, professor of medical physics at the University of Wisconsin-Madison. By serial imaging the radiation emitted by the targeted radionuclide therapy, this group was able to determine how much and when the radiation would be delivered to a tumor and other normal tissues, they explained in the publication Science Translational Medicine. .

The revealing data turned out that mice given doses too low to fight cancer produced a cure, when given alone, when given with immunotherapy.

This is why, Patel said, what they were able to observe was that low doses of radiation, not suited to destroying cancer, “stress the tumor cells” by stimulating the kind of response that the immune system has. usually occurs in the face of infection. So, driven by immunotherapy, immune cells attacked cancer cells that had been damaged by radiation therapy. In addition, when tumor cells were reintroduced into mice cured by the combination therapy, they quickly fought them off and no longer developed cancer.

“Treatment with low doses of radiation therapy and immunotherapy eradicated their cancer, and it also acted as a kind of cancer vaccine, preventing the mice from developing this type of cancer again,” Patel said.

The main study was done in mice, but then, together with David Vail’s team at the University of Wisconsin School of Veterinary Medicine, they tested the combination of targeted radiation therapy and immunotherapy. as a treatment in domestic dogs suffering from naturally occurring metastatic cancer. . The dogs tolerated this combination of treatment well, with no toxic side effects.

The next step will be for the authors seek approval from the United States Food and Drug Administration to begin testing this agent in human clinical trials.

“Human clinical trials are needed for our discovery to become a new standard of care. Meanwhile, the concept of this approach can now be tested in humans, using approved radiation therapies designed to target specific types of cancer, ”Patel said.

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