New genetic experiment shrinks hard-to-treat cancer

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

Kathy Wilkes is not cured but said what was left of her cancer had shown no signs of growing since the single treatment last June.

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

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

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

This is only a first step and a lot more research is needed, he warned – noting that Wilkes is one of only two people known to have tried this exact approach and failed at l other patient.

Still, Veatch said the results are “proof of principle that it’s possible” and that other researchers are also testing this type of immunotherapy.

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

But this CAR-T therapy does not work against more common solid tumors, which do not carry 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 spot a mutant protein hidden inside his tumor cells — and only there, not in healthy cells.

How? Certain molecules sit on the surface of cells and give the immune system insight into the proteins inside. If a complex receptor on the T cell recognizes both the person’s genetically distinct “HLA” molecule and one of the protein extracts embedded in it is the targeted mutant, this immune fighter can latch on.

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

Dr Eric Rubin, editor of the New England Journal, said the study raises the possibility of possibly being able to target several cancer-causing mutations.

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

Wilkes underwent chemotherapy, radiation and surgery for his pancreatic cancer. Later, doctors discovered new tumors in his lungs – pancreatic cancer had spread, a stage where there is no good treatment.

Wilkes knew researchers were testing immunotherapy to fight different hard-to-treat tumors, and a biopsy showed a specific mutation was fueling his cancer. His research led to Tran, who in 2016 co-authored a study on a subset of T cells that naturally harbor receptors capable of spotting this same so-called KRAS mutation.

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

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

Tran said it’s unclear 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 fueled by what Tran calls “hotspot” mutations.


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

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