Genetically Engineered Immune Cells Found to Rapidly Clear Leukemia Tumors

The new therapy for acute lymphoblastic leukemia, a swift-growing cancer that tends to kill more than 60 percent of those afflicted, involves extracting T cells and modifying them to home in on and destroy B cells in healthy and cancerous tissue

By Heidi Ledford and Nature magazine

Blood cells from a patient suffering from chronic lymphocytic leukemia, seen on peripheral blood film. Image: Flickr/Ed Uthman

Genetically engineered immune cells can drive an aggressive type of leukemia into retreat, a small clinical trial suggests.

The results of the trial ? done in five patients with acute lymphoblastic leukemia ? are published in Science Translational Medicine and represent the latest success for a 'fringe' therapy in which a type of immune cell called T cells are extracted from a patient, genetically modified, and then reinfused back. In this case, the T cells were engineered to express a receptor for a protein on other immune cells, known as B cells, found in both healthy and cancerous tissue.

When reintroduced into the patients, the tricked T cells quickly homed in on their targets. ?All of our patients very rapidly cleared the tumor,? says Michel Sadelain, a researcher at the Memorial Sloan-Kettering Cancer Center in New York and an author of the study. The treatment ?worked much faster than we thought?.

The technique has already shown promise against chronic leukemia, but there were doubts about whether it could take on the faster-growing acute lymphoblastic leukemia, a tenacious disease that kills more than 60% of those afflicted. ?

Carl June, an immunologist at the University of Pennsylvania in Philadelphia and a pioneer in engineering T cells to fight cancer, says that he is surprised that the method worked so well against such a swift-growing cancer. The next step, he says, is to move the technique out of the ?boutique? academic cancer centers that developed it and into 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.

Extra hope
Oncologist Renier Brentjens, also at Memorial Sloan-Kettering Cancer Center, remembers the day that he had to tell one of the patients in the trial that the weeks of high-dose chemotherapy the 58-year-old man had endured had not worked after all. ?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.?

Another month in the hospital on intensive chemotherapy drugs did nothing to help. By the time the man started the trial, 70% of his bone marrow was tumor.

Brentjens, Sadelain and their colleagues then extracted T cells from the patient and engineered them to express a ?chimeric antigen receptor?, or CAR, that would target cells expressing a protein called CD19. Because CD19 is found on both healthy and cancerous B cells, the engineered T cells were unable to discriminate between the two. However, patients can live without B cells.

By two weeks after the procedure, the patient was showing signs of improvement. The treatment had driven his cancer into remission ? as it did for the other four patients in the trial ? so he became eligible for a bone-marrow transplant. A hundred days later, he is doing well, says Brentjens. Four of the five patients were well enough to receive transplants; the remaining patient relapsed and was ineligible.

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