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Immune-system therapy shows promise in adults with leukemia

By Sharon Begley

NEW YORK (Reuters) - An experimental therapy that tweaks cancer patients' own immune cells to recognize an often-deadly form of leukemia has shrunk tumors and sent the cancer into remission in adults, according to a U.S. study published on Wednesday.

Although a similar immune-system approach has shown promise in children with this cancer as well as in adults with a related form of leukemia, it is the first time this particular therapy has worked in adults.

Scientists said the finding, which was based on a study of five adults, had "life-saving potential." The study was published in the journal Science Translational Medicine.

The experimental therapy targeted acute lymphoblastic leukemia (ALL), a blood-cell cancer that often proves resistant to chemotherapy and can kill in mere weeks. It is more common in children but especially deadly when it occurs in adults.

Although current treatments cure an estimated 80 percent to 90 percent of children with ALL, they are effective in only 30 percent or fewer of adult cases, said Dr. Michel Sadelain of Memorial Sloan-Kettering Cancer Center in New York, co-leader of the study.

Adults whose ALL has returned after being temporarily beaten back with chemotherapy, Sadelain and his colleagues wrote, "have a dismal prognosis."

The study adds to the evidence that harnessing the immune system to destroy tumors could turn back many cancers.

For instance, a therapeutic vaccine against deadly melanoma, called Yervoy and manufactured by Bristol-Myers Squibb, was approved in 2011, and scores of other immune-system-based drugs to treat cancer are in the pipeline. IMS Health has estimated that global sales of immune-based oncology drugs could reach $75 billion by 2015.

In the new study, scientists started with their patients' T cells, a form of white blood cell. These foot soldiers of the immune system make a beeline for both viruses and cancer cells, which sport molecules that act like homing beacons to attract the T cells.

Normal T cells find and attack only invaders studded with homing beacons they're able to recognize. That's why the immune system does not sweep out all cancers, let alone viruses such as HIV: T cells have not been trained to detect their beacons.

The scientists therefore re-trained the T cells to do so.

After extracting T cells from patients with ALL, a process that takes a few hours, the scientists mixed them with a harmless virus that inserted genes for a three-part molecule: one part that trains T cells to recognize homing beacons on the leukemic cells, called CD19; one part that instructs T cells to kill any such cells they find; and one part that makes T cells survive longer than usual.

After 10 to 12 days, the T cells were now genetically-engineered to detect those beacons. The cells were then returned to their five patients, aged 23, 58, 56, 59 and 66.

"The T cells are living drugs," said Sadelain. "They see the CD19, they kill the cancer cells, and they persist in the body."

Four of the patients' leukemia became undetectable in 18 to 59 days. One patient achieved the remission eight days after treatment - a dramatic result considering that several of the patients had bone marrow "chock full of leukemia," Sadelain said.

But the treatment wasn't always easy on patients. After one got back his genetically-engineered T cells, he developed a 105 degree fever as the T cells ignited what's called a cytokine storm, in which cytokines - hormones - are produced in vast quantities, leading to plummeting blood pressure and spiking fever. A second patient also suffered this cytokine storm, but in both cases it was managed with steroids.

The researchers are raising funds for a larger study, with 50 patients or more, at Sloan-Kettering as well as other cancer centers, including the Dana-Farber Cancer Institute in Boston.

They already have successfully treated three additional patients beyond the five described in the paper, Dr. Renier Brentjens of Sloan-Kettering said, and suspect they might get even better results if they began treatment earlier in the disease.

(Reporting by Sharon Begley; Editing by Jilian Mincer and Paul Simao)

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