Cells reprogrammed to fight cancer
Ken Shefveland’s body was swollen with cancer, treatments failing until doctors removed some of his immune cells, engineered them into cancer assassins and unleashed them into his bloodstream.
Immune therapy is the hottest trend in cancer care and this is its next frontier — creating “living drugs” that grow inside the body into an army that seeks and destroys tumours.
Shefveland said “the cancer was just melting away.” A month later doctors at the Fred Hutchinson Cancer Research Center couldn’t find any signs of lymphoma in the Vancouver, Wash., man’s body.
“Today I find out I’m in full remission — how wonderful is that?” said Shefveland.
This experimental therapy marks an entirely new way to treat cancer — if scientists can make it work, safely. Early stage studies are stirring hope as one-time infusions of supercharged immune cells help a remarkable number of patients with intractable leukemia or lymphoma.
“It shows the unbelievable power of your immune system,” said Dr. David Maloney, Fred Hutch’s medical director for cellular immunotherapy who treated Shefveland with a type called CAR-T cells.
“We’re talking, really, patients who have no other options, and we’re seeing tumours and leukemias disappear over weeks,” added immunotherapy scientific director Dr. Stanley Riddell. But “there’s still lots to learn.”
T cells are key immune system soldiers. But cancer can be hard for them to spot, and can put the brakes on an immune attack. Today’s popular immunotherapy drugs called “checkpoint inhibitors” release one brake so nearby T cells can strike. The new cellular immunotherapy approach aims to be more potent: Give patients stronger T cells to begin with.
Currently available only in studies at major cancer centres, the first CAR-T cell therapies for a few blood cancers could hit the market later this year. The U.S. Food and Drug Administration is evaluating two different versions.
CAR-T therapy “feels very much like it’s ready for prime time” for advanced blood cancers, said Dr. Nick Haining of the DanaFarber Cancer Institute and Broad Institute of MIT and Harvard, who isn’t involved in the development.
Now scientists are tackling a tougher next step, what Haining calls “the acid test”: Making T cells target far more common cancers — solid tumours like lung, breast or brain cancer. Cancer kills about 600,000 Americans a year, and approximately 79,000 in Canada.
Scientists still are unravelling why these living cancer drugs work for some people and not others.
Doctors must learn to manage potentially life-threatening sideeffects from an overstimulated immune system. Also concerning is a small number of deaths from brain swelling, an unexplained complication that forced another company, Juno Therapeutics, to halt development of one CAR-T in its pipeline; Kite recently reported a death, too.
“It’s a Model A Ford and we need a Lamborghini,” said CAR-T researcher Dr. Renier Brentjens of New York’s Memorial Sloan Kettering Cancer Center, which, like Hutch, has a partnership with Juno.
At a recently opened Seattle immunotherapy clinic, scientists are taking newly designed T cells from the lab to the patient and back again to tease out what works best.
“We can essentially make a cell do things it wasn’t programmed to do naturally,” explained immunology chief Dr. Philip Greenberg. “Your imagination can run wild with how you can engineer cells to function better.”
TWO LONG WEEKS TO BREW A DOSE
When leukemia patient Claude Bannick entered a Hutch CAR-T study in 2014, nurses hooked him to a machine that filtered out his white blood cells, including the T cells.
Technicians raced his bag of cells to a factory-like facility that’s kept so sterile they must pull on germdeflecting suits, booties and masks just to enter. Then came 14 days of wait and worry, as his cells were reprogrammed.
Bannick, 67, says he “was almost dead.” Chemotherapy, experimental drugs, even a bone-marrow transplant had failed, and “I was willing to try anything.”
WHAT’S THE DATA?
Small, early studies in the U.S. made headlines as 60 per cent to 90 per cent of patients trying CAR-Ts as a last resort for leukemia or lymphoma saw their cancer rapidly decrease or even become undetectable. Recently, Chinese researchers reported similar early findings as 33 of 35 patients with another blood cancer, multiple myeloma, reached some degree of remission within two months.
Too few people have been studied so far to know how long such responses will last. A recent review reported up to half of leukemia and lymphoma patients may relapse.
There are long-term survivors including Doug Olson who in 2010 received the University of Pennsylvania’s CAR-T version for leukemia.
Bannick, the Hutch patient treated in 2014, had some lingering sideeffects but says CAR-T is “giving me a second life.”
As CAR-T cells swarm the cancer, an immune overreaction called “cytokine release syndrome” can trigger high fevers and plummeting blood pressure and in severe cases organ damage. Some patients also experience confusion, hallucinations or other neurologic symptoms.
FIGHTING SOLID TUMOURS WILL BE HARDER
CAR-Ts cause collateral damage, killing some healthy white blood cells, called B cells, along with cancerous ones because both harbour the same marker. Finding the right target to kill solid tumours,but not healthy organ tissue, will be even more complicated.
“This is the hope of any cancer patient, that if you stay in the game long enough, the next treatment’s going to be just around the corner,” said Shefveland.
Doctors reprogram patients’ cells to turn them into cancer fighters, Lauran Neergaard writes.
Ken Shefveland has had some of his immune cells reprogrammed into an army of “living drugs” to better destroy his cancer.
Cell production associate Herley Beyene, left, places containers of immune cells in a centrifuge at the Fred Hutchinson Cancer Research Center in Seattle. Researchers are genetically reprogramming patients’ immune cells to create “living drugs” that help fight cancer. Right: Research technician Ashwini Balakrishnan works in the immunotherapy research lab at the centre.