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Engineered immune cells battle Leukemia

March 20, 2013 This article courtesy of Nature News.

T cells altered to seek and destroy acute blood cancer.

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Genetically engineered immune cells can drive an aggressive blood cancer into retreat, suggests a small clinical trial in five patients with acute leukemia.

The results of the trial, published today in Science Translational Medicine, are the latest in a series of successes for a “fringe” therapy in which a patients’ own T cells are extracted, genetically modified, and then reinfused. In this case, the T cells were engineered to express a receptor that targets B cells, including the cancerous B cells driving the leukemia.

When reintroduced into the patients, the tricked out T cells quickly homed in on their targets. “All of our patients very rapidly cleared the tumour,” says Michel Sadelain, a cancer researcher at the Memorial Sloan-Kettering Cancer Center in New York and a lead author on the study. “It worked much faster than we thought.”

The technique has already shown promise against slower growing chronic leukemia in adults and children, but there were doubts about whether it could take on the fleet-footed acute lymphoblastic leukemia, a tenacious disease that ultimately kills over 70% of those afflicted.  

Carl June, a cancer immunologist at the University of Pennsylvania in Philadelphia and a pioneer in engineering T cells to fight cancer, says he was surprised the method worked so well against such a swift-growing cancer. The key, he says, is now to move it out of the ‘boutique’ academic cancer centers that have developed the method and into more standard clinical care in multicenter clinical trials.

“What needs to be done is to convince oncologists and cancer biologists that this new kind of immunotherapy can work,” he says.

Bad news

Oncologist Renier Brentjens, also of Memorial Sloan-Kettering Cancer Center, remembers the day that he delivered the bad news to patient #5 on the trial. Weeks of high dose chemotherapy had seemed to work for the 58-year-old man. But the cancer came back. “It was painful to have that conversation,” says Brentjens. “He tells me now it was the worst news he has ever heard in his life.”

Over a month in the hospital on intense chemotherapy drugs did nothing to help. By the time he started the T-cell trial, patient #5’s bone marrow was 70% tumour.

Brentjens, Sadelain, and their colleagues extracted T cells from patient #5 and engineered them to express a ‘chimeric antigen receptor’ (CAR) that would target cells expressing a protein called CD19 that is expressed on both healthy and cancerous B cells. The engineered T cells do not discriminate between the two, but patients can live without B cells.

Export control

Two weeks after the procedure, patient #5 was showing signs of improvement.  Like the other four patients on the trial, the treatment drove his cancer into remission, making him eligible for a bone marrow transplant. A hundred days later, he is doing well, says Brentjens.

Pharmaceutical firms have long been wary of the CARs technique because it is technically challenging, must be personalized for each patient, and faces an untested path to regulatory approval, says Steven Rosenberg, a cancer researcher at the National Cancer Institute in Bethesda, Maryland. But there are signs that this is changing: Rosenberg points to a recent collaboration between Swiss pharmaceutical giant Novartis and June’s group, as well as the launch of several small CARs-focused biotechnology firms. And Sadelein notes that he is an investigator on a trial with the Dana Farber Cancer Institute in Boston, Massachusetts, which, in part, will test whether the technique can be exported to new sites.

Brentjens, meanwhile, is happy to have his patients in fighting spirits again. “You see these people at their lowest low emotionally as well as physically,” he says. “And now you can tell they’re in better shape because they’re making fun of your tie again.”

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