In a new experiment, a woman with advanced pancreatic cancer saw her tumors shrink sharply after Oregon researchers overloaded her own immune cells, revealing a possible new way to treat her someday. various cancers.
Kathy Wilkes is not cured, but said the remainder of her cancer has shown no signs of growth since the single treatment last June.
“I knew that regular chemotherapy wouldn’t save my life, and I was going to save it,” said Wilkes of Ormond Beach, Florida, who located a scientist thousands of miles away and asked him to try. experiment.
The research, published Wednesday in the New England Journal of Medicine, explores a new way to harness the immune system to create “living drugs” capable of searching for and destroying tumors.
“It’s really exciting. This is the first time this type of treatment has worked in a type of cancer that is very difficult to treat, “said Dr. Josh Veatch of the Fred Hutchinson Cancer Research Center in Seattle, who did not participate in the experiment.
It’s just a first step and much more research is needed, he warned, noting that Wilkes is one of only two people known to have tried this exact approach and failed the other patient.
However, Veatch said the findings are “proof of principle that this is 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 escapes them. Doctors have already learned how to strengthen T cells to fight some types of leukemia and lymphoma. They add an artificial receptor to patients’ T cells so that immune fighters can recognize a marker on the outside of the blood cells and attack them.
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 modified Wilkes’ T cells so that they could detect a mutant protein that hides inside their tumor cells. and only there, not in healthy cells.
How? Some molecules are located on the surface of cells and give the immune system a look at what proteins are inside. If a complex T-cell receptor recognizes both the person’s genetically different “HLA” molecule and one of the protein fragments embedded in it is the target mutant, that immune fighter can be caught.
It is 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 are on the right track.”
Dr. Eric Rubin, editor-in-chief of the New England Journal, said the study raises the possibility that it could eventually lead to multiple mutations that cause cancer.
“We’re talking about the opportunity to distinguish tumor cells from non-tumor cells in a way we could never before,” he said.
Wilkes underwent chemotherapy, radiation and surgery for his pancreatic cancer. Doctors later discovered new tumors in his lungs: pancreatic cancer had spread, a stage in which there is no good treatment.
Wilkes knew that researchers were testing immunotherapy to fight different tumors that were difficult to treat, and a biopsy showed that 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 detecting the same mutation called KRAS.
Wilkes also had the right type of HLA molecule. Thus, Tran and her colleague Dr. Rom Leidner, an oncologist, obtained permission from the Food and Drug Administration to reprogram their T cells to carry the special anti-mutant receptor. .
They extracted T cells from Wilkes’ blood, genetically modified 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 reviews show that her disease remains stable.
Tran said it is unclear why the experiment failed in another patient, although lessons from this case led to 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 collaboration with the Howard Hughes Medical Institute Department of Science Education. The AP is solely responsible for all content.