Revolutionary cancer treatment wakes up immune system to destroy tumors

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CAMBRIDGE, Mass. — A revolutionary cancer treatment is combining several therapies to successfully destroy tumors, scientists from the Massachusetts Institute of Technology say. Their breakthrough treatment “jump starts” a patient’s natural defenses by merging chemotherapy, immunotherapy, and tumor-fighting techniques.

Using this novel approach, researchers say diseased cells are removed from the body, treated with drugs, and then placed back in the tumor. They are delivered with a payload of medications that activate the immune system’s T cells. The injured cancer cells appear to act as a distress signal that spurs them into action.

“When you create cells that have DNA damage but are not killed, under certain conditions those live, injured cells can send a signal that awakens the immune system,” says senior author Professor Michael Yaffe in a university release.

An effective cancer treatment for many types

Immunotherapy – which stimulates the immune system to kill tumors – only works for a handful of cancers. The new method could enable it to be used against many forms of the disease.

In experiments, it completely eliminated tumors, melanomas, and breast cancers in 40 percent of treated mice. When the same rodents were injected with cancer cells months later, T cells recognized and destroyed them before new tumors could form.

The MIT team improved the performance of immunotherapy drugs called checkpoint blockade inhibitors. They take the brakes off of T cells that have become “exhausted” and unable to attack tumors. Adding chemotherapy drugs helped injured cells send signals that attract the immune system’s attention.

“This describes a new concept of immunogenic cell injury rather than immunogenic cell death for cancer treatment,” Prof. Yaffe reports.

“We showed that if you treated tumor cells in a dish, when you injected them back directly into the tumor and gave checkpoint blockade inhibitors, the live, injured cells were the ones that reawaken the immune system.”

Several clinical trials combining the therapies are underway. The study in the journal Science Signaling sheds fresh light on the best approach.

Striking the right cancer-killing balance

The drugs that worked best were those that cause DNA damage. They activate cellular pathways in tumors that respond to stress. The chemicals send out distress signals that provoke T cells to destroy injured cells and any other tumor cells nearby.

“Our findings fit perfectly with the concept that ‘danger signals’ within cells can talk to the immune system, a theory pioneered by Polly Matzinger at NIH in the 1990s, though still not universally accepted,” the study author adds.

Researchers also tried injecting DNA-damaging drugs directly into the tumors, instead of treating cells outside the body. However, this was ineffective because the chemotherapy drugs also harmed T cells and other immune cells near the tumor.

Also, injecting the injured cells without checkpoint blockade inhibitors had little benefit.

“You have to present something that can act as an immunostimulant, but then you also have to release the preexisting block on the immune cells,” Prof. Yaffe concludes.

Yaffe now hopes to test the approach in patients whose tumors have not responded to immunotherapy. First, study authors will need to carry out more tests to determine which drugs, and at which doses, would be most beneficial for different types of tumors.

The researchers are also further investigating exactly how the injured tumor cells stimulate such a strong T cell response.

South West News Service writer Mark Waghorn contributed to this report.





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