Experimental immune-system therapy offers new hope for leukemia patients

Robin Wulffson MD's picture
acute lymphoblastic leukemia, ALL, treatment, immune system, T cells

Adults with B cell acute lymphoblastic leukemia (B-ALL) have a dismal prognosis if the blood cancer relapses following treatment. A new experimental therapy that stimulates the patients’ own immune cells to recognize the malignant cells has shrunk tumors in these patients and sent the cancer into remission. The findings were published on March 20 in the journal Science Translational Medicine by researchers affiliated with Memorial Sloan-Kettering Cancer Center (New York, New York) and the University of Texas Southwestern (Dallas, Texas).

Previously, a similar immune system approach was reported to have promise for children with this cancer as well as in adults with a related form of leukemia; however, the authors note that iti is the first time this particular therapy has worked in adults. The investigators describe that their findings have “life-saving potential.” The experimental therapy targeted B-ALL, a blood-cell cancer that often proves resistant to chemotherapy and can kill in mere weeks. It is more common in children; however, it is particularly deadly when it occurs in adults.

Current treatments cure an estimated 80-90% of children with B-ALL, they are effective in only 30% or fewer of adult cases, noted col-leader Dr. Michel Sadelain of Memorial Sloan-Kettering Cancer Center. He notes that the study adds to the evidence that harnessing the immune system to destroy tumors could turn back many cancers. He explains that a therapeutic vaccine against deadly melanoma, called Yervoy and manufactured by Bristol-Myers Squibb, was approved in 2011. In addition, a number of other immune-system-based drugs to treat cancer are in the pipeline.

The basis of the study was the patients’ own immune cells: T cells, which are a form of white blood cell. These cells recognize both viruses and cancer cells and destroy them. However, the T cells only attack cells, which contain molecules that act like homing beacons to attract the T cells. Cancer cells and viruses, such as HIV, do not have these homing beacons; thus, the T cells do not seek out and destroy them. In the study, the researchers trained the T cells to seek out and destroy these invaders.

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After extracting T cells from patients with B-ALL, the researchers mixed them with a harmless virus that inserted genes for a three-part molecule: one part that trains T cells to recognize homing beacons on the leukemic cells, called CD19; one part that instructs T cells to kill any such cells they find; and one part that makes T cells survive longer than usual. After a period of 10 to 12 days, the T cells were now genetically-engineered to detect those beacons. The cells were then returned to their five patients, aged 23, 58, 56, 59, and 66.

“The T cells are living drugs,” explained Dr. Sadelain. He added, “They see the CD19, they kill the cancer cells, and they persist in the body.” Four of the patients’ leukemia became undetectable in 18 to 59 days. One patient achieved the remission eight days after treatment. Dr. Sadelain described this as a dramatic result because several of the patients had bone marrow “chock full of leukemia.”

On the downside, the treatment was hard on the patients. After one received his genetically-engineered T cells, he developed a 105 degree fever as the T cells ignited what is termed a cytokine storm, in which cytokines (hormones) are produced in vast quantities, leading to plunging blood pressure and soaring fever. A second patient also suffered this cytokine storm; however, in both cases, the problem was managed with steroids.

The researchers note that a larger study is necessary; thus, they are raising funds for a larger study, with 50 patients or more, at Sloan-Kettering as well as other cancer centers, including the Dana-Farber Cancer Institute in Boston. They already have successfully treated three additional patients beyond the five described in the paper and suspect they might get even better results if they began treatment earlier in the disease.

Reference: Science Translational Medicine