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发帖数: 29846 | 1 By
Ron Winslow
Feb. 19, 2014 6:59 p.m. ET
A technique to genetically modify a patient's own immune cells eradicated
tumors in 14 of 16 patients with advanced leukemia—at least for a time—in
a study that adds to growing enthusiasm for efforts to enlist the body's
immune system in the fight against cancer.
The findings, from researchers at Memorial Sloan-Kettering Cancer Center,
also add fuel to an emerging race to bring new so-called cancer
immunotherapy treatments to the market. Juno Therapeutics Inc., a Seattle
startup, is preparing to launch a mid-stage, or phase 2, study of the
treatment based on the results of the new study. Novartis SA plans a phase 2
trial of a similar strategy developed at the University of Pennsylvania.
The patients, all adults, were diagnosed with acute lymphoblastic leukemia,
or ALL, an especially aggressive disease, and all had relapsed after
standard therapy. About 6,000 cases of the cancer are diagnosed in the U.S.
each year, according to the American Cancer Society. About one third occur
in adults, for whom the prognosis typically poor.
The researchers had previously reported success in achieving complete
remissions in five of the patients. The new study, published Wednesday in
the journal Science Translational Medicine, includes 11 more patients. It
found that among all 16, 88% had a "complete response" to the treatment,
meaning researchers couldn't find any molecular evidence of disease, though
not all of the patients remained in remission.
"It was an impressive response rate in such a [sick] patient population,"
said Renier J. Brentjens, a medical oncologist at Sloan-Kettering and a
senior author of the study.
The treatment involved retrieving a patient's own T-cells, the infection-
fighting agents of the immune system, and modifying them genetically to
target a protein called CD19 that is present on ALL cells. Then the
engineered cells, called CAR T-cells (for chimeric antigen receptor) are
infused back into the patient, poised to hunt down the leukemia cells and
kill them.
The results of the new trial are strikingly similar to a study at University
of Pennsylvania presented at a medical meeting last December, in which 19
of 22, or 86%, children with ALL achieved complete remissions. They were
treated with a similar T-cell genetically altered to target CD19.
"These response rates are identical in children and adults in what was
previously regarded as a lethal tumor," said Carl June, a cancer researcher
leading the effort at Penn. The validation of the approach from two
different research groups is "great news for leukemia," he said.
One big question is how durable the response is. The longer-term outcomes
were also affected by the fact that some patients at Sloan-Kettering became
eligible for bone marrow transplants, which can offer a chance for prolonged
survival. "At that point, we weren't running an experiment, we were trying
to keep people alive," said Michel Sadelain, director of the Center for Cell
Engineering at Memorial Sloan Kettering and a senior author of the study.
Seven of the 16 patients underwent a transplant, two of whom died of
complications, and one is being evaluated for a transplant. Of the other
eight, four died, while four remain in remission, including one who remains
in remission more than two years after being treated.
As research progresses, researchers hope to learn more about how long the
treatment lasts for patients who don't get bone-marrow transplants,
potentially learning whether a transplant would be necessary.
Researchers said the study also provided information that might help
identify in advance patients who are likely to experience severe side
effects to the treatment that can require hospital care. The information
might enable preventive steps, including treatment with steroids, to reduce
the impact of the effects.
Write to Ron Winslow at r*********[email protected] |
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