cancer research

Ravi Patel, Indian American assistant professor at the University of Pittsburgh School of Medicine, and radiation oncologist at the UPMC Hillman Cancer Center. (UPMC photo)

Indian American-led research by teams from the University of Wisconsin at Madison and the University of Pittsburgh School of Medicine July 14 reported 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.

The study, led by Ravi Patel, assistant professor at Pitt and radiation oncologist at UPMC Hillman Cancer Center, was published in the journal Science Translation Medicine.

“We’re excited — with such low doses of radiation, we didn’t expect the response to be so positive,” Patel said in a statement. “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, a joint news release said.

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, the news release added.

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, the universities noted.

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, the release said.

Patel and Morris worked closely with a team of medical physicists led by Bryan Bednarz, a professor of medical physics at UW–Madison. By obtaining serial images of the radiation emitted by a targeted radionuclide therapy, this group was able to determine how much and when radiation would be delivered to a tumor and to other healthy tissues, the release adds.

To the researchers’ surprise, the mice given both immunotherapy and doses of targeted radionuclide therapy that were much too low to kill the cancer when given alone were the ones that were cured, it said.

Instead of destroying the tumors, Patel says, the low-dose radiation was “stressing cells in the tumor,” stimulating the tumor cells to activate a type of response that is more commonly seen in settings where cells have been infected by viruses. Boosted by the immunotherapy, the immune cells attacked the cancer cells that had been damaged by targeted radionuclide therapy, it adds.

Additionally, when tumor cells were reintroduced to the mice cured by the combination therapy, they quickly fought them off and did not develop cancer again, the release said.

“Treating with low-dose radiotherapy and immunotherapy not only eradicated their cancer, it acted as a sort of anti-cancer vaccine, preventing the mice from getting this type of cancer again,” Patel, who performed the research at UW–Madison as a Bentson Translational Research Fellow, added in the release.

A Madison-based start-up company, Archeus Technologies, is now completing studies needed to apply for approval from the Food and Drug Administration to begin testing this agent in human clinical trials.

“Human clinical trials are needed in order to develop our finding into a new standard of care,” Patel noted in the release. “In the meantime, the concept of this approach can be tested in humans now, using approved radiotherapies designed to target specific types of cancer.”

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