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Stephanie Florence recieves an infusion of CAR T immunotherapy nine years into her battle against “incurable” lymphoma. The treatment wiped out her cancer, even though it had persisted through all other treatments. (Photo courtesy of Stephanie Florence)

Nearly 40 years ago, scientists had what seemed like a crazy idea: What if we could reprogram cancer patients’ immune systems to wipe out their disease?

It turns out the idea wasn’t so crazy.

Stephanie Florence is living proof of that. She was 34 when she was diagnosed with a kind of blood cancer that is considered incurable. After fighting the disease for nine years, she was out of options. So she signed up for a clinical trial of an experimental cancer treatment called CAR T immunotherapy.

“I received my infusion on July 2,” Florence told GeekWire, recalling the life-changing treatment she received in 2015. “I had a scan on July 30 and I was supposed to find out the next day, but they called me that evening and told me that it was clear. That it was totally clear. I was in remission.”

CAR T immunotherapy is some of the most stunning science happening in cancer research. It is wiping out cancer in patients who are literally on death’s doorstep. But it wasn’t always this way.

On this episode of GeekWire’s Health Tech podcast, we trace the story of CAR T as it went from the black sheep of scientific research to a cancer killer. Listen to the episode in the player below, subscribe to the show in your favorite podcast app, and continue reading for more.

The science behind CAR T actually comes from another cancer treatment: Bone marrow transplants. Scientists like Dr. Stan Riddell, now the head of immunotherapy research at Seattle’s Fred Hutchinson Cancer Research Center, realized that the T-cells of bone marrow donors were able to detect and attack leukemia cells in the transplant recipients.

“We didn’t understand exactly how it worked, but what we knew is that the T-cells that were transplanted with the bone marrow graft were able to eliminate leukemia cells. And if you took those T-cells out, you lost that effect,” Riddell said. “I thought if we could really understand that, maybe there were ways of using T-cells… for cancer more broadly.”

T-cells are like the navy seals of the immune system: They find and destroy bugs that make you sick, like the flu. But they normally don’t attack cancer cells, which put up defenses against the immune system. In the 1980s, turning T-cells into cancer-killing machines seemed almost laughable.

Dr. Stan Riddell, an early CAR T immunotherapy researcher and now the scientific director of immunotherapy research at the Fred Hutchinson Cancer Research Center. (GeekWire Photo / Clare McGrane)

“A very large majority of the scientific community sort of viewed this as fringe research,” Riddell said.

But he and others persisted. Riddell discovered how to genetically modify T-cells to give them different receptors, sensors that tell the cell what to attack. But there was a big problem with this plan: No naturally occurring CAR T cells had receptors that target cancer.

The breakthrough came from another wing of science, called signaling. It’s the language that proteins in the human body use to talk to each other. And using this new understanding, Riddell and others were able to use signaling to create man-made receptors, called chimeric antigen receptors, or CARs.

Over the past four decades, immunologists across the globe put these puzzle pieces together and refined the science to create today’s CAR T therapies. Patients only started taking CAR T treatments a few years ago, but so far the results have been stunning.

“In [acute myeloid leukemia] our complete remission rate is over 90 percent, which is extraordinary,” Riddell said. “That means taking a patient whose bone marrow is riddled with leukemia and essentially eradicating all detectable leukemia cells from the bone marrow with a single infusion of cells. You just don’t see those kinds of results with a therapy that’s new that you’re putting into patients for the first time.”

For patients with non-Hodgkin Lymphoma, Florence’s cancer, the results are still impressive: 40 percent of patients who have taken the drug went into remission, even though they failed all other treatment options.

“I remember them bringing in my bag of T-cells and it was so tiny… it was like, ‘that’s my life hanging there'”, Florence said. “I don’t even know how to put it into words how ecstatic I was that I had been given a second chance.”

But not all patients respond to the treatments, and in some cases, they can even have deadly side effects. Juno Therapeutics, a spin-out of the Fred Hutch, was forced to pull its leading CAR T therapy last year after five patients in a clinical trial died from serious side effects.

Those side effects have popped up in patients taking almost every CAR T currently being tested, although they are becoming better controlled and less severe. Despite the setback, Juno was acquired by Celgene last year for $9 billion.

Today, two CAR T treatments have been approved by the FDA: One made by Novartis that treats leukemia and lymphoma and one made by Kite Pharma, which has since been bought by Gilead Sciences for $11 billion, that treats lymphoma.

And this is the major stumbling block for CAR T: It works incredibly well in patients with blood cancers, but solid tumors like breast and lung cancer are much more difficult to treat. Even for patients with blood cancer, the treatment doesn’t always work or the cancer will return after a few years.

“We need to understand why we’re not eradicating all of the tumor cells in those patients and what we can do to improve that. And that’s a focus of a lot of the work right now,” Riddell said.

Another stumbling block is the treatment’s astoundingly high price tag.

Stephanie Florence, left, celebrated the infusion of her CAR T treatment with family, tiaras and party hats. (Photo courtesy of Stephanie Florence)

“I think the price is really one of the, one of the major crisis that we’re facing,” said Dr. David Maloney, the scientific medical director of the Bezos Family Immunotherapy Clinic. The clinic, which opened at the Seattle Cancer Care Alliance in December 2016, was the first in the world to be dedicated to CAR T immunotherapy treatment.

“These drugs are expensive. The published prices for these drugs are around $373,000 for the lymphoma drug and actually higher for the leukemia drug, and that’s a huge amount of money,” he said. Novartis’ leukemia CAR T treatment costs $475,000.

Becuase of that price, the treatments are only realistically available to patients who have insurance willing to cover it.

But despite these problems, CAR T therapy seems to be here to stay. It’s part of a growing trend of using the immune system to fight cancer in a variety of ways. Other immunotherapy drugs, like checkpoint inhibitors, have found success in recent years, including the drug that wiped out the cancer of former U.S. President Jimmy Carter.

And although many scientists avoid using the word ‘cure,’ it seems CAR T therapy could be a key to finding that holy grail of cancer research.

“Immunotherapy, if we look at it in general, I think will play a major role in achieving cures,” Riddell said. “I think it may, in some ways, be essential to cure cancer. You may need to develop an immune response against the cancer.”

And regardless of how the science works out, Florence said that hope can make all the difference for patients.

“I no longer feel like I’m incurable,” she said. “And regardless of what happens with CART, if that winds up being cured for me or if it winds up being a cure for patients down the road — I, for the first time, feel like there is a chance for a cure.”

Editor’s Note: This story has been updated to reflect the FDA approval of Novartis’ CAR T treatment. It has been approved to treat both leukemia and lymphoma.

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