Fresh frontier in cancer care: Turning blood into living drugs
Arrest made in connection to GR drug bust
Another arrest was made in connection to a big drug bust in Grand Rapids that resulted in one of the defendants being shot.
GVSU student protected under DACA vows to ‘keep fighting’
A Grand Valley State University student protected under DACA is now facing an uncertain future.
Crime lab at home of Wyoming man tied to missing mom
Muskegon-area shelter welcomes animals of Harvey
Police searching for missing teenage damsel
Weather
Current Conditions
- Feels Like: 62° F
- Wind: W 17
- Humidity: 56%
- Dewpoint: 46° F
- Sunrise: 7:11 AM
- Sunset: 8:09 PM
Grand Rapids Weather
Sports
Latest Headlines
WMU moves on to MSU after near-upset
Western Michigan almost pulled off the unlikely last Saturday.
Verlander to make Astros debut in Seattle
Former Detroit Tiger pitcher Justin Verlander will be pitching Thursday, but for the very first time in his career, not in a Tigers uniform.
Ribbon-cutting held at Detroit’s Little Caesars Arena
Arizona’s JD Martinez hits four home runs, ties MLB record
Steelers RB Le’Veon Bell comebacks to work
eightWest
Latest Headlines
AARP and the City of GR team up to make community livable for all ages
Do you have ideas on how to make Grand Rapids friendlier for all ages?
Soaring Eagle welcomes Ron White to the stage come October
Soaring Eagle has some amazing shows coming to their stage this fall.
Practice high flying adventures right here in West Michigan
Prevent illness this school year; flu shot clinics at Spectrum Health
Grand Sea Hotel: fresh event space for West Michiganders
Community
Latest Headlines
Aquinas to Host National Lacrosse Invitational
The college is set to host its very first national tournament in two thousand eighteen and 2019.
KCAS Pets of the Week: Rodney and Shadow
Meet Rodney and Shadow, this week’s adoptable pets of the week from the Kent County Animal Shelter.
Recovering from Harvey: How you can help
Treat yourself to a night of glitz and glamour at Metro Health’s VITALity Gala
Rev up, car paramours: The 13th annual Metro Cruise is here
Fresh frontier in cancer care: Turning blood into living drugs
Related Coverage
‘Sci-fi’ cancer therapy fights brain tumors, examine finds
Colorectal cancer uncommon but rising among millennials, Gen X
Dying from cancer: Could your location determine your fate?
SEATTLE (AP) – Ken Shefveland’s bod was engorged with cancer, treatment after treatment failing until doctors gambled on a radical treatment: They liquidated some of his immune cells, engineered them into cancer assassins and released them into his bloodstream.
Immune therapy is the greatest trend in cancer care and this is its next frontier — creating “living drugs” that grow inwards the assets into an army that seeks and demolishes tumors.
Looking in the mirror, Shefveland spotted “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, Washington, man’s assets.
“Today I find out I’m in total remission — how wonderful is that?” said Shefveland with a broad sneer, providing his physician a quick embrace.
This experimental therapy marks an entirely fresh way to treat cancer — if scientists can make it work, securely. 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, truly, patients who have no other options, and we’re witnessing tumors and leukemias vanish 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 fresh cellular immunotherapy treatment aims to be more potent: Give patients stronger T cells to begin with.
Presently available only in studies at major cancer centers, the very first CAR-T cell therapies for a few blood cancers could hit the market later this year. The Food and Drug Administration is evaluating one version developed by the University of Pennsylvania and licensed to Novartis, and another created by the National Cancer Institute and licensed to Kite Pharma.
CAR-T therapy “feels very much like it’s ready for prime time” for advanced blood cancers, said Dr. Nick Haining of the Dana-Farber 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 tumors like lung, breast or brain cancer. Cancer kills about 600,000 Americans a year, including almost 45,000 from leukemia and lymphoma.
“There’s a desperate need,” said NCI immunotherapy pioneer Dr. Steven Rosenberg, pointing to queries from hundreds of patients for studies that accept only a few.
For all the excitement, there are formidable challenges.
Scientists still are unraveling why these living cancer drugs work for some people and not others.
Doctors must learn to manage potentially life-threatening side effects from an overstimulated immune system. Also concerning is a petite number of deaths from brain full salute, an unexplained complication that coerced another company, Juno Therapeutics, to halt development of one CAR-T in its pipeline; Kite recently reported a death, too.
And, made from scrape for every patient using their own blood, this is one of the most customized therapies ever and could cost hundreds of thousands of dollars.
“It’s a Model A Ford and we need a Lamborghini,” said CAR-T researcher Dr. Renier Brentjens of Fresh York’s Memorial Sloan Kettering Cancer Center, which, like Hutch, has a partnership with Juno.
In Seattle, Fred Hutch suggested a behind-the-scenes peek at research underway to tackle those challenges. At a recently opened immunotherapy clinic, scientists are taking freshly designed T cells from the lab to the patient and back again to taunt 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
The very first step is much like donating blood. When leukemia patient Claude Bannick entered a Hutch CAR-T explore 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 germ-deflecting suits, booties and masks just to come in. Then came fourteen 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 attempt anything.”
GENETICALLY ENGINEERING CELLS
The purpose: Arm T cells with an artificial receptor, a tracking system that can zero in on identifying markers of cancer cells, known as antigens. For many leukemias and lymphomas, that’s an antigen named CD19.
Every research group has its own recipe but generally, scientists infect T cells with an inactive virus carrying genetic instructions to grow the desired “chimeric antigen receptor.” That CAR will tie to its target cancer cells and rev up for attack.
Millions of copies of engineered cells are grown in incubators, Hutch technicians pulling out precious batches to monitor if they’re ready for waiting patients.
If they work, those cells will keep multiplying in the bod. If they don’t, the doctors send blood and other samples back to researchers like Riddell to figure out why.
WHAT’S THE DATA?
Puny, early studies in the U.S. made headlines as sixty percent to ninety percent of patients attempting CAR-Ts as a last resort for leukemia or lymphoma eyed their cancer rapidly decrease or even become undetectable. Last week, Chinese researchers reported similar early findings as thirty three of thirty five patients with another blood cancer, numerous 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 latest review reported up to half of leukemia and lymphoma patients may relapse.
There are long-term survivors. Doug Olson in two thousand ten received the University of Pennsylvania’s CAR-T version for leukemia. The researchers were frank — it had worked in mice but they didn’t know what would happen to him.
“Sitting here almost seven years later, I can tell you it works,” Olson, now 70, told a latest meeting of the Leukemia and Lymphoma Society.
Bannick, the Hutch patient treated in 2014, recalls Maloney calling him “the miracle man.” He had some continuous side effects that required blood-boosting infusions but says CAR-T is “giving me a 2nd life.”
SCARY SIDE EFFECTS
“The more side effects you have, that sort of tells everybody it’s working,” said Shefveland, who was hospitalized soon after his treatment at Hutch when his blood pressure collapsed. His last clear memory for days: “I was having a conversation with a nurse and all of a unexpected it was gibberish.”
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 harm. Some patients also practice confusion, hallucinations or other neurologic symptoms.
Treatment is a balancing act to control those symptoms without shutting down the cancer attack.
Experienced cancer centers have learned to expect and observe for these problems. “And, most importantly, we’ve learned how to treat them,” said Dr. Len Lichtenfeld of the American Cancer Society, who is watching CAR-T’s development.
FIGHTING SOLID TUMORS WILL BE Stiffer
CAR-Ts cause collateral harm, killing some healthy white blood cells, called B cells, along with cancerous ones because both harbor the same marker. Finding the right target to kill solid tumors but not healthy organ tissue will be even more complicated.
“You can live without some normal B cells. You can’t live without your lungs,” Riddell explained.
Early studies against solid tumors are beginning, targeting different antigens. Time-lapse photos taken through a microscope in Riddell’s lab display those fresh CAR-T cells crawling over aggressive breast cancer, releasing toxic chemicals until tumor cells shrivel and die.
CARs aren’t the only treatment. Researchers also are attempting to target markers inwards tumor cells rather than on the surface, or even gene mutations that don’t form in healthy tissue.
“It’s ironic that the very mutations that cause the cancer are very likely to be the Achilles heel,” NCI’s Rosenberg said.
And studies are beginning to test CAR-Ts in combination with older immunotherapy drugs, in hopes of overcoming tumor defenses.
HOW WILL PATIENTS GET THE Very first CAR-T THERAPIES?
If the FDA approves Novartis’ or Kite’s versions, eligible leukemia and lymphoma patients would be treated at cancer centers experienced with this tricky therapy. Their T cells would be shipped to company factories, engineered, and shipped back. Little by little, more hospitals could suggest it.
Because only certain patients would qualify for the very first drugs, others would have to search for CAR-T studies to attempt the treatment. A drug industry report lists twenty one CAR-T therapies in development by a dozen companies.
“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, the Hutch patient.
– This Associated Press series was produced in partnership with the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content
