By Michael Irving
Scientists have supercharged immunotherapy by engineering CAR T cells that can produce their own “medicine” to keep them fighting in the hostile environment around tumors
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A new form of immunotherapy helps immune cells “armor” themselves against exhaustion by releasing their own medicine to keep them going in the fight against cancer. In a small ongoing trial, 100% of patients have achieved complete remission, and the new method is faster and cheaper to produce than existing immunotherapies.
The immune system is still our best weapon in the war against cancer, but it can be outsmarted by this crafty foe. Immunotherapy is an emerging treatment that can help us regain the upper hand, by removing immune cells from patients, supercharging them against cancer, then returning them to the body to get to work.
The technique has shown promise in humans, particularly against liquid cancers, but they’ve had mixed results against solid tumors so far. Much of the problem arises from the fact that the modified immune cells, known as Chimeric Antigen Receptor (CAR) T cells, become exhausted in the stressful environment around a tumor, losing their effectiveness and allowing the cancer to bounce back. A major area of research now is in finding ways to rejuvenate CAR T cells with stem cells or molecules, or by blocking proteins or genes that slow them down.
In the new study, scientists at EPFL have developed a new way to bolster CAR T cells against exhaustion. The team engineered the cells to excrete a molecule called interleukin-10 (IL-10), which helps them continue to proliferate and function near tumors – basically, the researchers say, the immune cells are producing their own medicine to keep them going in the hostile environment tumors create around themselves.
In tests in mice, the team showed that IL-10 CAR T cells completely cleared out a range of different cancer types, including melanoma, colon, breast and pancreatic cancers. Even when cancer cells were later reintroduced into the animals, the vigilant immune cells prevented them from establishing new tumors.
“We’ve added another layer to the CAR-T cell therapy by bioengineering a more robust, supercharged immune cell that is particularly efficient at targeting and destroying tumor cells,” said Professor Li Tang, co-author of the study.
In a clinical trial of the treatment, all 11 patients reportedly achieved complete remission so far, although the trial is still ongoing.
Along with the improved effectiveness, the IL-10 CAR T cell immunotherapy boasts other advantages too. A much smaller amount of modified cells is needed – just 5% of a usual dose for other immunotherapies. That drastically reduces the cost, which can reach into the hundreds of thousands of dollars, and time of the procedure, which can take weeks or even months to grow enough cells from a sample.
“A small amount of blood from a patient could provide already enough cells to prepare CAR-T cell therapy with our technology,” said Tang. “The next day you can already inject them back to the patient. It will be substantially less expensive and much faster to produce, saving more lives in the end.”
The research was published in the journal Nature Biotechnology.
Source: EPFL
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