Novel genetic experiment shrinks hard-to-treat cancer


Novel genetic experiment shrinks hard-to-treat cancer

In a novel experiment, a woman with advanced pancreatic cancer saw her tumors shrink dramatically after researchers in Oregon supercharged her own immune cells, showing a possible new avenue to one day treat a variety of cancers.

Kathy Wilkes isn’t cured but said the remains of her cancer hadn’t shown any signs of growth since being treated once last June.

“I knew that regular chemotherapy wasn’t going to save my life, and I wanted to save,” said Wilkes of Ormond Beach, Fla., who tracked down a scientist thousands of miles away and asked him to try the experiment.

The study, published Wednesday in the New England Journal of Medicine, examines a new way to use the immune system to create “living drugs” capable of seeking out and destroying tumors.

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

It’s only a first step, and far more research is needed, he warned – noting that Wilkes is one of only two people known to have tried this exact approach, and he with the other patient failed.

However, Veatch said the results are “principle proof that this is possible” and that other researchers are also testing this type of immunotherapy.

T cells are important immune soldiers, capable of killing diseased cells — but too often cancer eludes them. Doctors have already learned how to boost T cells to combat some types of leukemia and lymphoma. They add an artificial receptor to the patient’s T-cells so that the immune fighters can recognize and attack a marker on the outside of the blood cancer cells.

But this CAR-T therapy does not work against more common solid tumors that do not have the same danger marker.

The new twist: At the Providence Cancer Institute in Oregon, researcher Eric Tran genetically engineered Wilkes’ T cells so they could discover a mutated protein hidden in their tumor cells — and only there, not in healthy cells.

As? Certain molecules sit on the surface of cells and give the immune system a taste of what proteins are inside. When a complex receptor on the T cell recognizes both the person’s genetically distinct “HLA” molecule and that one of the protein snippets embedded within it is the targeted mutant, this immune fighter can take hold.

It’s an approach known as T cell receptor or TCR therapy. Tran stressed that the research remains highly experimental, but said Wilkes’ remarkable response “gives me optimism that we’re on the right track.”

dr Eric Rubin, senior editor of the New England Journal, said the study raises the possibility of eventually being able to target multiple cancer-causing mutations.

“We’re talking about the chance to differentiate tumor cells from non-tumor cells in a way that we never could before,” he said.

Wilkes underwent chemotherapy, radiation and surgery for her pancreatic cancer. Doctors later discovered new tumors in her lungs – the pancreatic cancer had spread, a stage where there is no good treatment.

Wilkes knew researchers were testing immunotherapy to target various difficult-to-treat tumors, and a biopsy showed a specific mutation was fueling her cancer. Her search led to Tran, who in 2016 co-authored a study on a subset of T cells that naturally contained receptors capable of recognizing the same mutation called the KRAS.

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

They took T cells from Wilkes’ blood, genetically engineered them in the lab, and then grew billions of copies. Six months after a transfusion of the altered cells, her tumors had shrunk by 72% – and Wilkes said recent research shows her disease remains stable.

Tran said it’s not clear why the experiment failed in another patient, although lessons from that case led to some changes in Wilkes’ treatment.

The Oregon team opened a small study to further test TCR therapy for patients with incurable cancers caused by so-called “hot spot” mutations.


This Associated Press series was produced in partnership with the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.

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