Gene Therapy Kills Leukemia Tumors

Thursday, 11 August 2011 07:24 AM

Two leukemia patients were cancer-free in three weeks after being treated with genetically engineered versions of their own immune cells, an early finding that could lead to a new approach for treating the blood cancer.

The trial of three patients showed that researchers could reprogram enough infection-fighting T-cells to wipe out malignant cells. The procedure also stimulated cells that defend against the cancer’s return, according to papers published today in Science Translational Medicine and the New England Journal of Medicine.

The results may point researchers to a new way to cure chronic lymphocytic leukemia, researchers said. The only method for achieving remission is a bone marrow transplant, which carries a 20 percent death risk and offers a cure half the time, said Carl June, a professor of pathology and laboratory medicine at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia and a study author.

“In a way, this is like a bone marrow transplant where the patient is the donor,” June said in a telephone interview. “This might make treatment more widely available with less long-term toxicity.”

The third patient was in partial remission and has remained there for seven months, the study showed. All of the patients had previously been treated with cancer drugs such as Biogen Idec Inc.’s and Roche Holding AG’s Rituxan, and Sanofi’s Campath.

About 14,990 new cases of chronic lymphocytic leukemia were diagnosed in 2010, and about 4,390 people died from the blood cancer, according to the National Cancer Institute.

Reprogrammed T-Cells

From the blood of the three patients, scientists extracted T-cells, white blood cells that attack and destroy infectious invaders. Using a genetic-engineering technique, the researchers reprogrammed the T-cells to specifically target the leukemia cells. The T-cells were also instructed to divide in the presence of the cancer, a feat that previously had been difficult to achieve in other attempts to modify T-cells, the study said. That allowed the modified T cells to build an army to destroy the cancer.

“This is pretty cool,” said David Steensma, an associate professor of medicine at Harvard Medical School and an oncologist at Dana-Farber Cancer Institute. He wasn’t involved in the study. The army of T-cells “not only has attacked and cleared the field but it’s also set up a patrol to make sure the enemy doesn’t come back.”

Still in Remission

When the white blood cells were returned to the patients, they experienced “the worst flu of their lives,” said June. The patients experienced fevers, chills, nausea, and diarrhea — signs that the new T-cells were working. One patient developed a disorder that makes it difficult for the immune system to make antibodies.

At 28 days after the first infusion, the cancer was undetectable. The patients have remained in remission so far.

“You have to be careful using the word ‘cure’ because we’re looking at a few patients,” said Richard Winnecker, the vice president of research for the Leukemia and Lymphoma Society. He wasn’t involved in the study. “We need to be careful until there’s more data, but this looks really encouraging.”

The results suggest a similar technique could be used in other cancers, such as lung and ovarian cancer, and myeloma and melanoma, according to the papers.

The method also stimulates so-called memory T-cells, which may help protect patients against the cancer’s return, the studies said.

Other Cancers

June is testing the same technique in other cancers, targeting proteins in pancreatic cancer, ovarian cancer, and mesothelioma, he said. Other groups are testing in prostate cancer and brain cancer.

The technique isn’t yet commercial, June said. He owns patents on the method.

“I want to make sure it gets FDA (Food and Drug Administration) approved, so there has to be a company involved,” June said. “It’s at an early stage so we’ll see what the industry does, whether we’ll work with an existing company or a new start-up, I don’t know yet.”

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Thursday, 11 August 2011 07:24 AM
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