In a medical breakthrough scientists have found that gene therapy could be used to cure leukemia. Researchers at the University of Pennsylvania engineered patients' own pathogen-fighting T-cells to target a molecule found on the surface of leukemia cells. These genetically modified T-cells were grown outside of the body and infused back into patients suffering from late-stage chronic lymphocytic leukemia (CLL), which affects the blood and bone marrow and is the most common form of leukemia.
The phase 1 trial included three participants of which two after therapy have been in remission for up to a year. The third participant had a strong anti-tumor response, and his cancer remains in check. The research group plans to treat four more patients with CLL before moving into a larger Phase II trial.
Dr. Michael Kalos, director of translational and correlative studies at the University of Pennsylvania's Perelman School of Medicine and an investigator on the study said, “We put a key onto the surface of the T-cells that fits into a lock that only the cancer cells have.” The results provide “a tumor-attack roadmap for the treatment of other cancers,” including those of the lung and ovaries as well as myeloma and melanoma, researchers said. Kalos said past efforts to use the technique, known as “adoptive T-cell transfer,” failed either because the T-cell response was too weak or proved too toxic for normal tissue.
The findings were published simultaneously Wednesday in the New England Journal of Medicine and Science Translational Medicine.
The treatment appears safe, but researchers said more study was needed. The leukemia patients in the Phase I trial had to be treated with an immunity-boosting drug since the targeted molecule, CD-19, is also present on certain normal immune-system cells. About two weeks after the gene therapy, patients began to experience “tumor lysis syndrome” - chills, nausea and fever - caused by the break-down products of dying cancer cells. The engineered T-cells were detected in patients' blood for several months afterward, and a portion of them turned into “memory T-cells,” which could provide ongoing protection against cancer recurrence, researchers surmised.
Dr. Walter Urba of the Providence Cancer Center in Portland Oregon cautioned that continued presence of activated T-cells and memory cells might be more of a problem in other types of cancer where toxic effects on normal tissue could be more severe. In addition, the long-term viability of the treatment is still unknown. “One of the big questions is ... will those persistent T-cells continue to work and prevent that tumor from coming back,” said Urba, who was not involved in the study.
“We are looking for corporate partners as we head into Phase II trials,” Kalos said. Further study will show whether the latest results “reflect an authentic advance toward a clinically applicable and effective therapy or yet another promising lead that runs into a barrier that cannot be easily overcome,” Urba said in an NEJM editorial.
William Chambers, director of the Clinical Cancer Research and Immunology Program at the American Cancer Society said, “This approach to adaptive therapy with T cells is different and better [than previous immunotherapy attempts] because the cells are long-lived once they're transferred and active over a period of time. And it seems that a small number of them actually have a big impact. This is going to prove useful and important.”
“This is pretty cool,” said David Steensma, an associate professor of medicine at Harvard Medical School and an oncologist at Dana-Farber Cancer Institute. He wasn’t involved in the study. The army of T-cells “not only has attacked and cleared the field but it’s also set up a patrol to make sure the enemy doesn’t come back.”
“You have to be careful using the word ‘cure’ because we’re looking at a few patients,” said Richard Winnecker, the vice president of research for the Leukemia and Lymphoma Society, also not involved in the study. “We need to be careful until there’s more data, but this looks really encouraging.”
About 14,990 new cases of chronic lymphocytic leukemia were diagnosed in 2010, and about 4,390 people died from the blood cancer, according to the National Cancer Institute.
CRISPR-based therapy shown to be safe, effective for people with transthyretin amyloidosis