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March 22, 2013

Gene Therapy Potentially Cures Leukemia In Small Study



lymphoblastic leukaemia


 Medical Breakthrough
Scientists at Memorial Sloan-Kettering Cancer Center have released that cancer has been halted in five patients after treatment with own genetically modified cells. Results of the early-stage trial demonstrate that it may be possible to use gene-therapy techniques to control cancers in relapsed patients.
Anew cancer treatment has resulted in five patients experiencing complete remission of their disease with no detectable cancerous cells, scientists have announced.

Scientists at the Memorial Sloan-Kettering Cancer Center in New York developed a form of targeted immunotherapy based on inserting an additional gene into the patients' white blood cells that enabled these cells to identify and destroy any cancerous cells circulating in the bloodstream.

The patients had all experienced a serious relapse of a form of cancer of the white blood cells, called B-cell acute lymphoblastic leukaemia, before they received transfusions of their own immune cells that had been genetically modified with an extra cancer-fighting gene.

The new study, in five adults with acute leukemia in whom chemotherapy was unsuccesful, was published recently in the journal Science Translational Medicine.
Doctors treating the patients said that the results of the early-stage trial demonstrate that it may be possible to use the gene-therapy technique to control cancers in relapsed patients so that they can undergo a bone-marrow transplant with a donor's blood stem cells, leading to a complete cure.

The patients had initially undergone chemotherapy to control their cancers but, as so often happens, the disease returned and could not be treated further by the same approach because the cancerous cells had developed resistance to the drugs.

In adults, this type of leukemia is a “devastating, galloping disease,” said Dr. Michel Sadelain, the senior author of the new study and director of the Center for Cell Engineering and the Gene Transfer and Gene Expression Laboratory at Memorial Sloan-Kettering Cancer Center.

The treatment uses patients’ own T-cells, a type of white blood cell that normally fights viruses and cancer. The patient’s blood is run through a machine that extracts T-cells and returns the rest of the blood to the body. Researchers then do some genetic engineering: they use a disabled virus as a “vector” to carry new genetic material into the T cells, which reprograms them to recognize and kill any cell that carries a particular protein on its surface.

The protein, called CD19, is found on B-cells, which are part of the immune system. This target was chosen because the patients had a type of leukemia that affects B-cells, so the goal was to train the patients’ T-cells to destroy B-cells. Healthy B-cells — which make antibodies to fight infection — would be killed along with cancerous ones, but that side effect was treatable.

“We’re creating living drugs,” Dr. Sadelain said. “It’s an exciting story that’s just beginning.”

"Patients with relapsed B-cell acute lymphoblastic leukaemia resistant to chemotherapy have a particularly poor prognosis," said Renier Brentjens of the cancer center and lead author of the study.

"This ability of our approach to achieve complete remissions in all of these very sick patients is what makes these findings so remarkable and this novel therapy so promising," Dr Brentjens said.

Following the targeted immunotherapy, four of the five patients underwent a bone marrow transplant and to date three of these four have remained in remission for between five and 24 months - with one patient dying from complications unrelated to the cancer therapy.

"By serving as a bridge to stem-cell transplants, this therapy could potentially help cure adult patients with B-cell acute lymphoblastic leukaemia that has relapsed and who are chemotherapy resistant. Otherwise, these patients have a virtually incurable disease," Dr Brentjens said.

"We need to examine the effectiveness of this targeted immunotherapy in additional patients before it could potentially become a standard treatment for patients with relapsed B-cell acute lymphoblastic leukaemia," he said.

"Although this treatment may not itself be a cure, it does seem to be able to produce remissions in patients whose [cancer] has relapsed. This can then make patients eligible for stem cell transplantation - which can lead to a cure," Professor Brentjens said.


SOURCE  The Independent

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