Genetically engineered cell offers possible cancer-killing breakthrough
Research that changes a type of white blood cell so it's a weapon against cancer cells is being hailed by experts as a potential breakthrough in cancer research.
Scientists at the University of Pennsylvania turned T cells into cancer cell killers in a common type of leukemia using genetic engineering. Experts say it may be possible to engineer T cells to kill other types of cancer, including blood, breast and colon, as well.
The research, part of a very small clinical trial involving just three patients who had advanced cases of the chronic lymphocytic leukemia, is published online this week in the New England Journal of Medicine and also in Science Translational Medicine.
Two of the patients have been cancer-free for more than a year, while the other experienced improvements. The plan now, given such promising results, is to expand the trial and treat other patients, then follow them to see long-term effects, the researchers said. They also hope to test it in other, perhaps more aggressive cancers.
"This is a huge accomplishment — huge," Dr. Lee M. Nadler, dean for clinical and translational research at Harvard Medical School, told the Los Angeles Times. Nadler is credited with finding the molecule on cancer cells that the genetically engineered T cells attack.
The researchers said they added instructions to a virus for creating a molecule that binds to leukemia cells and tells the T cells to destroy them. In the clinical trial, they drew blood from the three patients who had chronic lymphocytic leukemia, infected the T cells with the virus and reinjected the blood back into the patients. The engineered T cells multiplied rapidly and killed the cancer cells, then remained for months. "They even produced dormant 'memory' T cells that might spring back to life if the cancer was to return," wrote the Times' Eryn Brown.
A CBS/Associated Press story said the therapy "resulted in armies of serial killer cells that targeted and destroyed cancer cells, even new cancer cells as they emerged. T cells typically attack viruses that way," but it noted study author Dr. Carl June, professor of pathology and laboratory medicine at the University of Pennsylvania, said it's the first time it has been turned against cancer.
The study describes what happened after the engineered T cells were reinjected in the patient. After 13 days, "the patient began having chills and low-grade fevers associated with grade 2 fatigue. Over the next five days, the chills intensified and his temperature escalated to 102.5 degrees," they wrote, noting he suffered a variety of miserable digestive symptoms, including nausea and diarrhea. But within slightly more than three weeks of having the modified cells reintroduced, "there was no evidence of (the leukemia) in the bone marrow." Ten months out, when the study was written, that patient remained cancer free.
The researcher believe that each engineered T cell killed 1,000 cancer cells or more. They noted that the engineered cells remained for six months at high levels in the blood and bone marrow and while there they continued to express the chimeric antigen receptor.
Bone marrow transplants have been the best hope for patients suffering from chronic lymphocytic leukemia and have been the only hope for an actual cure. But the side effects have been potentially serious, even fatal, including infections and liver and lung damage. About 20 percent of those who receive such a transplant may die of complications of those side effects, rather than the leukemia that was being treated.
Dr. David Porter, director of the blood and marrow transplant program at the Hospital of the University of Pennsylvania and a study co-author, told the Los Angeles Times that earlier efforts to modify T cells have been disappointing. It was different this time because the researchers added more instructions to the virus telling the cells to "multiply, survive and attack more aggressively."
The National Cancer Institute describes leukemia as "cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream." It says 44,000 new cases are diagnosed each year and about 22,000 people die from the disease. The institute also offers an online guide to the disease and its treatments.
The Mayo Clinic says that the form of leukemia called chronic lymphocytic leukemia affects a group of white blood cells called lymphocytes, which help the body fight infection.
One of the patients, who asked not to be identified, issued a statement through the university. He said chemotherapy worked for years, but it stopped. Now, he wrote, "I'm healthy and still in remission. I know this may not be a permanent condition, but I decided to declare victory and assume that I had won."
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