Experimental approach to treating pancreatic cancer heralded as a success
A new gene therapy shrank the tumors of a woman with pancreatic cancer. Researchers think it has the potential to benefit millions more.
An experimental treatment appears to have been successful in halting the progression of one woman’s advanced pancreatic cancer, doctors reported Wednesday in the New England Journal of Medicine.
The apparent success of the therapy — which involves tweaking the genes of immune cells so that they attack tumor cells — could be a major step forward in the treatment of not only pancreatic cancer, but other cancers as well.
“I’m really excited about this,” said Dr. Carl June, who more than a decade ago pioneered a different type of immune therapy for certain blood cancers. June was not involved with the new report.
Kathy Wilkes, 71, of Ormond Beach, Florida, was diagnosed with pancreatic cancer in early 2018. She initially underwent at least eight rounds of chemotherapy, as well as radiation and an operation called a Whipple procedure to remove part of her pancreas.
Within a year, however, the cancer had spread to her lungs.
“When I talked to my hometown oncologist and asked him what to do, he only had one answer, and that was chemotherapy. And I said, ‘That’s not my answer,’” Wilkes told NBC News.
She found a 2016 case report, also published in the New England Journal of Medicine, that detailed how a person with advanced colon cancer had been helped by an experimental type of gene therapy targeting a cancer mutation called KRAS G12D.
“I thought, ‘That is the trial I want.’ I knew that that was the trial that was going to save me, save my life. I just had that feeling,” Wilkes said.
With that in mind, she reached out to the author of the report, Eric Tran. Tran was at the National Institutes of Health when he treated the colon cancer patient, but had since moved on to the Providence Cancer Institute in Portland, Oregon. That’s where Wilkes found him and inquired about undergoing the same type of therapy.
It turned out that Wilkes had the same genetic mutation as the colon cancer patient, despite having different forms of cancer. Tran, who was involved with her therapy, was also an author of the latest New England Journal report.
Turning immune cells into tumor hunters
The experimental approach involved taking a sample of Wilkes’ T cells, a type of immune cell that attacks invaders in the body. Scientists then genetically modified these cells, reprogramming them to recognize and attack tumor cells.
The T cells were then multiplied billions of times in a lab, before being delivered back in Wilkes’ body via a single intravenous infusion.
The approach is reminiscent of CAR-T therapy, the form of treatment developed by June at the University of Pennsylvania.
“This is potentially a one-and-done treatment,” Dr. Rom Leidner, a co-author of the new report and co-director of the head and neck cancer therapy program at the Providence Cancer Institute, said of the new therapy.
Wilkes’ infusion was on June 14, 2021. Within a month, the tumors in her lungs shrank by more than half, the report found. Six months later, the tumors were reduced by 72 percent of their original size.
It is unclear how long the treatment may last, however.
Wilkes says her cancer remains stable, but she will undergo additional testing and scans this month as part of an annual update.
Pancreatic cancer is one of the deadliest forms of the disease. It’s rarely found before it spreads and therefore is more difficult to treat. Only about 11 percent of patients are expected to survive five years after diagnosis, according to the American Cancer Society.
Another patient with pancreatic cancer who received the same treatment at the Providence Cancer Institute did not survive. It’s unclear why the treatment seems to have been successful in one person but failed in another.
“We are working hard on trying to answer that question,” Tran said. “If we understand the mechanism, that could help us develop better therapies.”
“An encouraging result”
Wilkes’ doctors were able to target her tumors thanks to a mutation called KRAS. While a majority of pancreatic cancers have a KRAS mutation, Tran said that just about 4 percent of pancreatic cancer patients have the specific subtype of the mutation that would respond to this particular therapy.
But the mutation is not limited to just pancreatic cancer, said Dr. Eric Rubin, the New England Journal of Medicine’s editor-in-chief. The therapy, he said, therefore has the potential to be used against a variety of cancers.
“This particular mutation is common in tumors that arise from epithelial cells, such as lung, ovarian and pancreatic cancers,” Rubin said during a media briefing Wednesday. “We for the first time have an approach that could allow the treatment of a large variety of tumors beyond the small number of tumors that CAR-T cells can be used in a very specific type of immunotherapy.”
Still, Rubin stressed caution. “It was an encouraging result, but it’s certainly far from a cure,” he said.
Much more research is certainly needed, experts agree. Tran and Leidner are now recruiting patients for a Phase 1 clinical trial to continue investigating the therapy.
One potential factor that could explain Wilkes’ positive results is that her pancreatic cancer had spread to her lungs rather than her liver, said Dr. Ryan Carr, a pancreatic cancer expert at the Mayo Clinic in Rochester, Minnesota. Carr, who wasn’t involved with Wilkes’ treatment, said that in his experience patients whose tumors spread to the lungs tend to have more favorable outcomes than patients whose cancer spreads to the liver, a more common site of metastasis.
“In most situations, when we have these lung metastases, they don’t really cause symptoms in the patient,” Carr said. “It’s still a poor prognosis, but we know there’s something different about them, and they are a little bit better off than those that spread to the liver.”
June said he’s had the same experience.
As such details are worked out, both June and Carr maintain that the new therapy seems to be a major step forward in the treatment of pancreatic cancer.
“I think cancer research is going to pick up again and going to build on this,” said June, who is director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania. “The real question is not if but when this kind of therapy becomes a reality of curing patients with now lethal cancers.”
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