New genetic trial shrinks hard-to-treat cancer

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

Kathy Wilkes has not been cured but said the rest of the cancer has shown no sign of growth since a one-time treatment last June.

“I knew regular chemotherapy wouldn’t save my life, and I was going to 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 way to harness the immune system to produce “live drugs” capable of finding and destroying tumors.

“It’s really exciting. It’s the first time this type of treatment has been successful in a type of cancer that is very difficult to treat,” said Dr. Josh Fitch of the Fred Hutchinson Cancer Research Center in Seattle, who was not involved in the trial.

He cautioned that it is only a first step and more research is needed – noting that Wilkes is one of only two people known to have tried this delicate approach and failed in the other patient.

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

T cells are essential immune soldiers, able to kill diseased cells – but oftentimes cancer avoids them. Doctors have already learned how to do this T-cell strengthening To fight some types of leukemia and lymphoma. They add a synthetic receptor to patients’ T cells so that immune fighters can recognize and attack a marker on the outside of leukemia cells.

but that CAR-T . treatment It does not work against the most common solid tumors, which do not have the same danger sign.

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

How? Certain molecules are located on the surface of cells and give the immune system a peek at the proteins inside them. If there is a complex receptor in the T cell that recognizes both a person’s genetically distinct HLA molecule and one of the protein extracts embedded in it is the target mutant, that immune fighter can attach to it.

It’s an approach known as T-cell receptor therapy (TCR). Tran stressed that the research is still very empirical, but said Wilkes’ wonderful response “provides me with optimism that we are on the right track.”

Eric Rubin, editor-in-chief of the New England Journal of Medicine, said the study raises the possibility that we could eventually be able to target multiple cancer-causing mutations.

“We’re talking about an opportunity to differentiate cancerous cells from non-cancerous cells in a way we couldn’t before,” he said.

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

Wilkes knew that researchers were testing immunotherapy to fight various hard-to-treat tumors, and a biopsy showed that a particular mutation fueled the cancer. Her 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 so-called KRAS mutation.

Wilkes also had the right kind of HLA molecule. So Tran and colleague Dr. Rom Leidner, an oncologist, got FDA permission to reprogram their T cells to carry special mutation-resistance receptors.

They culled T cells from Wilkes’ blood, genetically engineered them in the lab and then cultured billions of copies. Six months after the modified cell transfer, her tumors had shrunk 72% — and Wilkes said recent scans showed her disease was still stable.

Tran said it’s not clear why the trial failed in another patient, though lessons from this case have led to some changes in Wilkes’ treatment.

Small Oregon team opened 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 partnership with the Howard Hughes Medical Institute’s Department of Science Education. AP is solely responsible for all content.