Gene therapy cures leukemia in 8 days (New Scientist magazine)

Gene therapy cures leukemia in eight days

• 26 March 2013 by Andy Coghlan
• Magazine issue 2910.

WITHIN just eight days of starting a novel gene therapy, David Aponte's "incurable" leukaemia had vanished. For four other patients, the same happened within eight weeks, although one later died from a blood clot unrelated to the treatment, and another after relapsing.

The cured trio, who were all previously diagnosed with usually fatal relapses of acute lymphoblastic leukaemia, have now been in remission for between 5 months and 2 years. Michel Sadelain of the Memorial Sloan-Kettering Cancer Center in New York, co-leader of the group that designed the trial, says that a second trial of 50 patients is being readied, and the team is looking into using the technique to treat other cancers.

The key to the new therapy is identifying a molecule unique to the surface of cancer cells, then genetically engineering a patient's immune cells to attack it.

In acute lymphoblastic leukaemia, immune cells called B-cells become malignant. The team were able to target a surface molecule known as CD19 that is only present on B-cells. Doctors extracted other immune cells called T-cells from the patients. These were treated with a harmless virus, which installed a new gene redirecting them to attack all cells bearing CD19. When the engineered T-cells were reinfused into the patients, they rapidly killed all B-cells, cancerous or otherwise.

"The stunning finding was that in all five patients, tumours were undetectable after the treatment," says Sadelain.

He reckons that the body should replenish the immune system with regular T-cells and healthy B-cells after a couple of months. However, the patients received donated bone marrow to ensure they could regrow a healthy immune system (Science Translational Medicine, doi.org/kwz).

The treatment is not the first to re-engineer T-cells to attack a form of leukaemia. Last year, an international company called Adaptimmune used the approach to treat 13 people with multiple myeloma – it left 10 in remission.

"Although it's early days for these trials, the approach of modifying a patient's T-cells to attack their cancer is looking increasingly like one that will, in time, have a place alongside more traditional treatments," says Paul Moss of Cancer Research UK.

Sadelain's team is now investigating the scope for attacking other cancers. Where no single surface molecule is unique to a cancer, he is seeking to target pairs of molecules that only occur together on cancer cells. In January, he demonstrated this approach by wiping out human prostate tumours implanted in mice, using T-cells engineered to target two surface molecules (Nature Biotechnology, doi.org/kw2).