Jun 2, 2022
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New genetic experiment shrinks intractable cancer

New genetic experiment shrinks intractable cancer

In a new experiment, a woman with advanced pancreatic cancer saw her tumors shrink dramatically after Oregon researchers turbocharged her own immune cells, suggesting a possible new way to treat various types of cancer.

Kathy Wilkes is not cured but says that after a single procedure last June, what’s left of her cancer is showing no signs of growing.

“I knew conventional chemotherapy wouldn’t save my life, and I wanted to be saved,” said Wilkes of Ormond Beach, Fla., who sought out the scientist thousands of miles away and asked him to run the experiment.

The study, published Wednesday in the New England Journal of Medicine, explores a new method of using the immune system to create “living drugs” that can seek out and destroy tumors.

“It’s really interesting. This is the first time that a treatment like this has worked for a very difficult-to-treat type of cancer,” said Dr. Josh Veitch of the Fred Hutchinson Cancer Research Center in Seattle, who was not involved in the experiment.

This is only the first step, and much more research needs to be done, he warned, noting that Wilks is one of only two people who have tried this approach and failed in another patient. However, Veitch said the results are “proof that it’s possible” and that other researchers are also testing this type of immunotherapy.

T cells are key soldiers of the immune system, capable of destroying diseased cells, but all too often cancer eludes them. Doctors have already learned how to strengthen T cells to fight certain types of leukemia and lymphoma. They add an artificial receptor to patients’ T cells so that immune fighters can recognize the marker on the outside of cancerous blood cells and attack them.

But this CAR-T therapy does not work against more common solid tumors that do not carry such a dangerous marker.

How? Certain molecules are found on the surface of cells and give the immune system an idea of ​​what proteins are inside. If a complex receptor on a T cell recognizes both a genetically distinct human HLA molecule and that one of the protein fragments inserted into it is a target mutant, an immune fighter can latch onto it.

This approach is known as T cell receptor therapy, or TCR. Tran stressed that the study remains highly experimental, but said that Wilks’ remarkable reaction “makes me optimistic that we are on the right track.”

Dr. Eric Rubin, editor-in-chief of the New England Journal, said the study raises the possibility that many cancer-causing mutations could eventually be targeted.

“We’re talking about being able to distinguish tumor cells from non-tumor cells in a way that we’ve never been able to do before,” he said.

Wilks underwent chemotherapy, radiation, and surgery for pancreatic cancer. Later, doctors discovered new tumors in her lungs – pancreatic cancer has spread, and this is a stage where there is no good treatment.

Wilkes knew that researchers were testing immunotherapy to fight various intractable tumors, and a biopsy showed that her cancer was caused by a specific mutation. Her search led to Tran, who in 2016 co-authored a study on a subset of T cells that naturally contain receptors that can detect that so-called KRAS mutation.

Wilkes also had the right type of HLA molecule. So Tran and his colleague Dr. Rom Leidner, an oncologist, got approval from the Food and Drug Administration to reprogram her T cells for a special mutant-fighting receptor.

They took T-cells from Wilks’ blood, genetically modified them in the lab, and then grew them into billions of copies. Six months after the transfusion of the altered cells, her tumors have shrunk by 72%, and according to Wilks, recent tests have shown that her disease remains stable.

It’s not yet clear why the experiment failed in the other patient, Tran said, although the lessons learned from that case have allowed some changes to be made to Wilks’ treatment.

The Oregon team has opened a small study to further test TCR therapy in patients with incurable cancers caused by mutations, which Tran calls “hot spots.”

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