In the all-hands effort to harness the powers of the immune system to fight cancer, scientists have reported that a new approach has eliminated all evidence of advanced-stage breast cancer in a 49-year-old woman who had run out of treatment options.
The patient’s “complete durable cancer regression” followed a single infusion of her own immune cells, which were painstakingly chosen for their ability to recognize and fight her tumors – then expanded into an army of nearly 100 billion identical cells.
More than three years later, the patient, Judy Perkins, is not only alive, but seemingly cancer-free, according to a report published Monday in the journal Nature Medicine.
“I have definitely hit the jackpot,” said Perkins, a retired engineer from Port St. Lucie, Fla.
When Perkins received her experimental therapy just before Christmas 2014, she said she sensed the optimism of the National Cancer Institute researchers who devised this new approach to immunotherapy.
The hand-selected immune cells “were their babies, growing in a lab for four months,” Perkins said. “The doctors were all excited.”
But having failed a dozen different treatments already, she was not so sanguine.
“I was just like: ‘Yeah, whatever. It probably won’t work, but maybe they’ll learn something, and it’ll help the next generation,’” she said.
But over the next five months, the infused tumor infiltrating lymphocytes, or TILs, survived, expanded and refused to let up on Perkins’ cancer, wherever they found it.
Chosen for their ability to home in on four mutant proteins present in all of her cancer cells, the TILs broke down and carried off the two large tumors growing on her chest wall, along with four tennis-ball-sized tumors lodged in her liver.
“Now,” Perkins said, “I’m the golden guinea pig.”
Indeed, Perkins’ response to the immunotherapy treatment is “unprecedented,” Laszlo G. Radvanyi of the Ontario Institute for Cancer Research wrote in a commentary that accompanies the study.
The success with Perkins’ breast cancer follows reports of similar responses in patients who had advanced-stage cancers of the bile duct, colon and cervix. All are examples of common cancers that don’t typically respond to other immunotherapies.
“This approach, while in its infancy, is capable of treating a wide variety of cancer types,” said Dr. Steven A. Rosenberg, an immunotherapy pioneer at the National Cancer Institute who led the team that treated Perkins.
If the labor-intensive approach could be adapted for delivery to hundreds of thousands of patients, it could give patients with advanced cancers “a very highly personalized treatment,” Rosenberg said.
The targeted nature of the experimental treatment also suggests it might spare cancer patients the debilitating side effects of chemotherapy, he added.
“It’s elegant in its simplicity,” said Dr. Crystal L. Mackall, founding director of Stanford University’s Center for Cancer Cell Therapy, who was not involved in the treatment.
In cancers such as those of the breast, colon and prostate, scientists have long detected that “there is some immune reaction,” Mackall said. “It’s just that it needs to be amplified.”
That’s exactly what the new treatment does. By finding, isolating and multiplying the tiny subset of immune cells that are still in the fight, then demonstrating their ability to vanquish a patient’s tumors, Rosenberg’s group has shown that “the cells are there,” Mackall said.
The prospects for turning this into a viable treatment for a huge population of cancer patients will hinge on whether scientists can find faster, simpler and cheaper ways to carry out each of the steps, she added.
“It’s labor-intensive,” she said. “But then, so is CAR-T therapy,” an immunotherapy type Mackall has helped develop. “There’s a lot of things we do in medicine that are complicated: if it works, you do it. We’re going to figure it out.”
In the fast-moving world of cancer research, the new report is being hailed as a development that could open a broad new front in cancer immunotherapy. Until now, existing immunotherapy drugs have shown little or no effectiveness against some of the most common cancers, including malignancies of the breast, prostate and colon.
One class of immunotherapy drugs already on the market – so-called “checkpoint blockade inhibitors” like Yervoy, Opdivo and Keytruda – lift the brakes on the immune system’s initial assault on cancer, a response mounted early in the disease that stops it for mysterious reasons.
For roughly one-third of patients with metastatic melanoma or advanced lung cancer, these drugs can drive cancer into remission. But they tend to work best on cancers that are influenced by environmental factors and are driven by lots of mutated genes.
In a very different type of immunotherapycalled CAR-T therapy, a patient’s T-cells, the warriors of the immune system, are removed, and then genetically reengineered in a lab to better recognize the patient’s own cancer. The fortified immune warriors are then expanded and reinfused into the patient.
The CAR-T approach appears to work largely on cancers of the blood and those that arise in children, malignancies that have relatively few mutations to serve as beacons for immune cells to home in on. Two CAR-T immunotherapy treatments have been approved for use by the Food and Drug Administration – Kymriah and Yescarta – but more are in the pipeline.
By most estimates, none of these immunotherapy drugs works well against the kinds of solid tumors that account for 90 percent of cancer deaths. For these cancers which have some but not lots of genetic mutations, the answer may be TILs, experts said.
“The majority of cancer patients still don’t respond to immunotherapy,” said Dr. Patrick Hwu, an oncologist and immunotherapy researcher at M.D. Anderson Cancer Center in Houston. “So that’s the huge area of need. And that lays the groundwork for why this may be so exciting.”
Hwu said that in addition to finding ways to make TIL therapy cheaper, faster and simpler to administer, researchers will need to figure out which patients are most likely to respond as dramatically as Perkins did.
“That’s the hard work that lies ahead,” said Hwu. “But it’s encouraging.”
By Melissa Healy (c)2018 Los Angeles Times, Distributed by Tribune Content Agency, LLC.