Gene Therapy Spurs Leukemia Hope

By Ron Winslow Wall Street Journal

Researchers reported fresh evidence Wednesday that using gene therapy to manipulate the immune system is emerging as a promising new strategy in the fight against cancer.

Five patients with a lethal leukemia achieved complete and rapid remissions after the treatment, in which cells from their own immune systems were genetically altered to specifically attack the disease.

While the study was small, researchers were impressed that the cancer was eradicated in all five patients. In one patient, all evidence of the cancer was gone eight days after treatment.

Five patients achieved rapid remission after their immune systems were manipulated.

“The results here are profound,” said Renier J. Brentjens, a medical oncologist at Memorial Sloan-Kettering Cancer Center, New York, and lead author of the study. “It’s a very promising step forward.”

The findings were reported in the journal Science Translational Medicine.

The patients, who ranged in age from 23 to 66, were diagnosed with acute lymphoblastic leukemia, or ALL, and had previously relapsed after standard chemotherapy. For such patients, a bone-marrow transplant is their only hope for a cure, and many don’t survive long enough to get one.

“This has the potential to increase the number of people who would be cured,” said Carl June, a cancer researcher at the University of Pennsylvania who wasn’t involved in the study. His own work with a similar technique has shown promise in chronic lymphocytic leukemia and in ALL in children.

The American Cancer Society estimates that 6,000 new cases of ALL will be diagnosed in the U.S. this year, one-third of them adults.

The treatment involves taking a patient’s T-cells, the infection- and disease-fighting cells of the immune system, and genetically modifying them to target a protein called CD19, which is present on ALL cells. The engineered cells are then infused back into the patient, primed to hunt down the leukemia cells.

In the current study, complete remission occurred within a maximum of 59 days of treatment, researchers reported. Two patients with especially advanced ALL experienced what Dr. Brentjens termed a “shake and bake response”—significant fever and a drop in blood pressure that resulted in their admission to intensive care.

The intensity of the side effects reflected both the patients’ level of disease as well as a dramatic response to the therapy, Dr. Brentjens said. They were effectively treated with steroids.

Researchers couldn’t measure how long the benefit would be sustained because once remission was established, four patients received bone-marrow transplants.

The fifth patient, who wasn’t a candidate for a transplant, relapsed after 90 days and eventually died, Dr. Brentjens said. One other patient died of a pulmonary embolism two months after a bone-marrow transplant.

More work is needed to determine how best to use the treatment in leukemia patients, Dr. Brentjens said. Meantime, his laboratory and others plan to test the strategy in a wide array of cancers.

Study sponsors included the National Cancer Institute and Sloan-Kettering. Dr. Brentjens and a co-author hold a patent on the engineered T-cell receptor.

A version of this article appeared March 21, 2013, on page A2 in the U.S. edition of The Wall Street Journal, with the headline: Gene Therapy Spurs Leukemia Hope.

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