University of Pennsylvania doctors have used gene therapy to train a patient’s own immune system to kill leukemia cells.
The New York Times reports that doctors gutted and reconstructed a disabled form of HIV-1 by selecting DNA from humans, mice and cows, a virus that infects woodchucks, and one that infects cows. The virus infects T-cells, a white blood cell that fights viruses and tumors, and alters the T-cells to reproduce chimeric antigen receptors, or CARS – protein complexes that transform the cells into “serial killers.” The T-cells recognize cancer, attack it, multiply, and continue to live on after the eradication of the cancer, patrolling the body to defend against relapses.
Doctors first tried the experimental treatment on William Ludwig, then a 65-year-old retired corrections officer from Bridgeton, NJ. Researchers passed Ludwig’s blood through a machine that removed about a billion T-cells before returning the blood back into his veins. The removed T-cells were introduced to the HIV virus, which infected and genetically transformed Ludwig’s T-cells, and then temporarily frozen. After chemotherapy to deplete any remaining T-cells that may have impeded the growth of the altered ones, the new T-cells were infused back into Ludwig’s blood.
Dr. Carl June, head of the research team, explains that, “The patient then becomes a bioreactor.” After 10 days, as the T-cells reproduced, Ludwig began shaking with chills, his temperature spiked, and his blood pressure dropped dangerously. The T-cells were producing chemicals called cytokines that caused flulike symptoms.
After a few weeks, the symptoms were gone, and with them, the leukemia. Ludwig’s doctors estimated that the treatment had killed two pounds of cancer cells in his blood.
Ludwig’s doctors cannot say that he is cured, as it has only been a year since the operation, but even Dr. June admits that he and his colleagues were stunned by the results. Although reconstructed HIV has been used to treat other diseases, never before has it been used to treat cancer.
Ludwig says that he feels wonderful, and is even walking through all 18 holes of golf. “I have my life back,” he says.
Since Ludwig, two other patients have been treated. One experienced full remission. When the other developed chills and fever, another hospital treated him with steroids, and may have disrupted the T-cells’ activity. Doctors also noted that his leukemia may have been too advanced. Still, he experienced partial remission.
Experts in the field said that the results signified a giant leap in molecular biology. Other cancers may also be vulnerable to the new treatment. Dr. June plans on next testing his team’s treatment against solid tumors, including hard-to-treat cancers like mesothelioma and ovarian and pancreatic cancer.