First long-term success for gene therapy cures leukemia

In the study the researchers used a disabled lentivirus to

introduce a gene into T-cells that would produce a protein 

on the cell surface that would lock on to the leukemic cells.

(Image provided by the National Institutes of Health)

For the first time a patient’s own cells have been successfully re-engineered to kill leukemia cells over a long period of time, researchers in Pennsylvania report.

In this first successful use of gene therapy to treat cancer, two people with advanced stage chronic lymphocytic leukemia have seen their cancers eliminated for more than a year, and a third has been living with the cancer held in check for that long.  Chronic lymphocytic leukemia, or CLL, is a common form of leukemia that causes over-production of non-functioning B-cells, the blood cells that normally protect the body with antibodies.

The research team led by Drs. David Porter, Michael Kalos and others reported the early results of the clinical trial simultaneously in today’s New England Journal of Medicine, and Science Translational Medicine.

In the small early-stage clinical trial designed to test the safety of the new therapy, researchers took a specific type of immune cells, called T-cells, from the patients’ own body and used a virus to re-engineer the cells’ DNA to produce a protein that specifically matches a receptor on leukemic cells. This allows T-cell lock onto the cancer cells and kill them.  The re-engineered cells are then grown in the laboratory into billions of copies and re-infused into the patient.
  

In the case of two patients, 14 days after the first infusion they began to experience the chills, nausea and fever associated with dying cancer cells, called tumor lysis syndrome. After 23 days there was no evidence of CLL in the bone marrow and 28 days after the infusion no swollen lymph nodes could be felt anywhere. A variety of tests were run to find cancer cells but none were detected. A CT scan performed a month after the infusion showed no areas of swollen lymph nodes.

Bone marrow studies at 3 and 6 months also showed no evidence of CLL using cell structure analysis, DNA analysis or cell identification analysis using flow cytometry. Remission has been sustained for 10 months as of this writing.

Before receiving the infusion of the altered T-cells researchers administer a round of chemotherapy using rituximab (Rituxan®) designed to deplete white blood cells, called lymphocytes. 

The tumor lysis syndrome can produce serious symptoms, with fevers of 102 and dehydration requiring hospitalization. In addition there was evidence of kidney damage that required treatment with medication to restore normal kidney function. Aside from that, there did not seem to be serious toxic side effects. 

Previous attempts at infusing changed T-cells resulted in only modest reduction in cancer that failed to be sustained over time. In this study, the altered T-cells seem to be persisting in the patients’ bodies, which is a cause of concern among some experts in the field. In an interview with Reuters, Dr. Walter Urba of the Providence Cancer Center in Portland, Oregon noted that the persistence of those altered T-cells poses an unknown potential for problems in the future. 

The study’s researchers caution that even though these results reflect a year-long experience, it is still only involves three patients and that many more will be needed to establish the effectiveness and short- and long-term side effects of this therapy.

Reuters

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