A therapy that reprograms patients' immune system's T cells to respond to cancers has had its long-term effectiveness confirmed. Although CAR T therapy's short-term success has been established for some time, leading to growing popularity, no one has been sure if the protection lasts, or if it's just a way to buy patients time as initially anticipated. A study of two patients who were among the first to receive T lymphocytes reprogrammed to fight their specific cancers has shown the cells maintain their presence and effectiveness more than a decade after the treatment. In CAR T cell therapy, patients' immune cells are collected and engineered to recognize cancer cells they would otherwise miss. Once primed, the T cells attack the cancer making it the first cell therapy made from the patient's own immune system. In Nature, the researchers responsible for some of the first applications of CAR T cell therapy report that more than ten years after treatment, no cancer cells can be detected in two patients' blood. Moreover, the CAR T cells remain capable of fighting cancer, as demonstrated when they were removed and exposed to cultured cancers. “It could be that every last cancer cell was gone within three weeks of when we treated [the patient],” Dr Carl June of the University of Pennsylvania told a press briefing. “Or it could be they keep coming up like wack-a-moles and get killed because these CAR T cells are on patrol.” Doug Olson, a patient diagnosed with chronic lymphocytic leukemia (CLL) at the age of 49, told the conference that after initial success with chemotherapy his condition declined until in 2010 the cancer made up half his bone marrow. He was offered a choice of a bone marrow transplant or the then experimental CAR T cells “I looked at [bone marrow transplant] as playing my last card,” Olson said. After an initial period of flu-like symptoms, the CAR T cells quickly came to make up a substantial proportion of the T cells in his body and within weeks he was completely free of cancer cells. June told the conference that CAR T therapy has been used for thousands of patients worldwide for acute leukemia since 2010, and is now approved in the US and UK for the more common lymphoma. Meanwhile, it is still in trials for a wider range of cancers, most recently multiple myeloma. “We can now conclude CAR T cells can actually cure patients of leukemia,” June said, although the authors acknowledged it does not work in every patient, even among those with the most susceptible forms of cancer. Nevertheless, it is one of the rare medical technologies that actually worked better in humans than in the animal models on which it was tested. “I think basically all blood cancers will be treated with CAR T cells over the next decade... because they're starting to move to frontline therapies, rather than end of the line therapy as Doug Olson had back in 2010 when there was basically nothing else left in the toolbox,” June said. “The big scientific challenge... is how to make this work in solid cancers.” Solid cancers make up around 90 percent of all cancers, June later noted. The authors acknowledge CAR T therapy is not side-effect free, with cytokine-release syndrome producing very high fevers, low blood pressure, and trouble breathing among other symptoms. Neurological side-effects are also experienced with patients finding it hard to think and speak. However, interventions have been developed that effectively treat cytokine-release syndrome, the authors claimed, making the therapies much safer over time. Meanwhile, the neurological side-effects, although more poorly understood, almost always resolve of their own accord. Olson, now running half-marathons, said he is not aware of any lingering side-effects of the treatment. A registry has been established of patients to look out for long-term effects such as auto-immune diseases, but so far none have been confirmed. CAR T therapy remains expensive, but the researchers anticipate the costs of producing the cells will fall significantly as it becomes more widely used. Source
