Combining low-dose radiotherapy with immunotherapy eradicates metastatic cancer in mice

Combining low-dose radiotherapy with immunotherapy eradicates metastatic cancer in mice

University of Wisconsin School of Medicine and Public HealthMore doesn’t necessarily mean better — including in cancer treatment.

University of Wisconsin–Madison and University of Pittsburgh School of Medicine scientists report today in the journal Science Translational Medicine that combining targeted radiopharmaceutical therapy with immunotherapy significantly boosts eradication of metastatic cancer in mice, even when the radiation is given in doses too low to destroy the cancer outright.

“We’re excited — with such low doses of radiation, we didn’t expect the response to be so positive,” says lead author Ravi Patel, assistant professor at Pitt and radiation oncologist at UPMC Hillman Cancer Center. “In clinical trials, we tend to go with the maximum tolerable dose, the idea being that radiation kills the cancer and the more we give, the better. But in this study our concept is different — we’re not trying to destroy the tumor with radiation, we’re trying to trigger the immune system to kill the cancer.”

Immunotherapy has revolutionized cancer treatment by helping patients’ immune systems fight off cancer. But some patients develop resistance to current immunotherapies and others have cancers characterized by immunologically “cold” tumors, which evade or suppress the patient’s immune response against his or her cancer.

In these cases, oncologists have found that external beam radiotherapy, or EBRT — where a patient is placed in a carefully calibrated machine that aims a beam of radiation directly at their tumor — can help turn “cold” or resistant tumors into “hot” tumors against which the immunotherapy treatments work better.

But EBRT cannot typically be delivered to all tumor sites in patients whose cancer has metastasized, or spread to other parts of their body, because distant tumors can be too small, plentiful and diffuse for the patient to tolerate so much radiation. In those cases, targeted radionuclide therapy can be an option. This treatment approach uses a radioactive element that is linked with a cancer-targeting molecule and given through an intravenous infusion, delivering radiation directly to the cancer cells upon decay of the radioactive element.

Patel, senior author Zachary Morris, a professor of human oncology in the University of Wisconsin School of Medicine and Public Health, and their colleagues designed a study to give mice with immunologically cold metastatic cancers varying doses of targeted radionuclide therapy alongside immunotherapy.