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 treats a variety of cancers.
Kathy Wilkes is not cured but said what is left of her cancer has shown no sign of growth since the single treatment last June.
“I knew regular chemotherapy wouldn’t save my life, and I went for the rescue,” said Wilkes of Ormond Beach, Florida, 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 using the immune system to create “living drugs” that can target and destroy tumors.
“It’s really exciting. It’s the first time this kind of treatment has worked in a very difficult-to-treat 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 much more research is needed, he cautioned — noting that Wilkes is one of only two people known to have tried this approach and failed in the other patient.
Still, Veatch said the findings are “a proof of principle that this is possible” and that other researchers are also testing this type of immunotherapy.
T cells are important immune soldiers that can kill diseased cells – but too often, cancer evades them. Doctors have already learned how to boost T cells to fight certain types of leukemia and lymphoma. They add an artificial receptor to patients’ T cells so that the immune fighters can recognize and attack a marker on the outside of blood cancer cells.
But that, CAR-T therapy doesn’t work against more common solid tumors, which don’t carry the same hazard marking.
The new twist: At the Providence Cancer Institute in Oregon, researcher Eric Tran genetically engineered Wilkes’ T cells so they could detect a mutated protein hidden in her tumor cells — and only there, not healthy cells.
How? Certain molecules sit on the surface of cells and give the immune system a taste of what proteins are inside. If a complex receptor on the T cell recognizes the person’s genetically distinct “HLA” molecule and that one of the protein fragments embedded in it is the targeted mutant, that immune fighter can latch on.
It is an approach known as T cell receptor or TCR therapy. Tran emphasized that the research remains highly experimental but Wilkes’ remarkable response “gives me optimism that we are on the right track.”
Dr. Eric Rubin, the editor of the New England Journal, said the study expands the possibility of eventually targeting multiple cancer-causing mutations.
“We’re talking about the opportunity to differentiate tumor cells from non-tumor cells in a way we’ve never been able to before,” he said.
Wilkes underwent chemotherapy, radiation, and surgery for pancreatic cancer. Later, doctors discovered new tumors in her lungs — pancreatic cancer had spread to a stage without proper treatment.
Wilkes knew that researchers were testing immunotherapy to fight several difficult-to-treat tumors, and a biopsy showed that 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 harbor receptors that can recognize that 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 her T cells to carry the special mutant-fighting receptor.
They extracted T cells from Wilkes’ blood, genetically engineered them in the lab, and grew billions of copies of them. Six months after a transfusion of the altered cells, her tumors had shrunk by 72% — and Wilkes said recent checkups show her disease remains stable.
Tran said it’s unclear why the experiment failed in another patient, although the lessons from that case prompted some changes in Wilkes’ treatment.
The Oregon team has opened a small study to further test TCR therapy for patients with incurable cancers fueled by what Tran calls “hot-spot” mutations.
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This Associated Press series was produced in conjunction with the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.
