Researchers have discovered how to turn CAR-T cells on and off that target tumor cells to destroy them, which could lead to better treatment of solid tumors.
- Scientists have discovered how to turn CAR-T cells on and off.
- CAR-T cells detect and target antigens, particularly present on the surface of tumor cells, to destroy them.
- This discovery could ultimately make it possible to better treat solid tumors by protecting healthy cells.
Between 1990 and 2023, the number of new cases of cancer doubled in France, according to the Panorama of cancers in France – 2023 edition. The increase is 98% in men and 104% in women, all locations combined. Faced with this growing phenomenon, the challenge of research is to treat patients as best as possible and, ultimatelyto heal them.
Turn CAR-T cells on and off
In a new study published in the journal Proceedings of the National Academy of Sciences and reported by EurekAlertscientists have discovered a way to activate and deactivate CAR-T cells, for Chimeric Antigen Receptor in English, T lymphocytes genetically modified to endow them with antigen receptors. This could ultimately make it possible to better treat solid tumors.
“Currently, CAR-T cells are already used to treat a number of blood cancers, but solid tumors continue to pose significant challenges for this mode of therapy in terms of safety and effectiveness, explains Melita Irving. We potentially addressed both of these issues by directly integrating on/off switches activated by drugs approved by regulators and already in clinical use into the CAR design.”.
Preserve healthy cells and limit T cell exhaustion
Currently, CAR-T cells detect and target antigens, particularly present on the surface of tumor cells, to destroy them. The problem is that many solid tumor antigens are also found on healthy cells. Thus, by targeting antigens, treatments can destroy healthy cells.
By developing this on/off function of CAR-T cells, researchers have therefore found a way to limit the risk for patients (by stopping treatment when healthy cells are attacked) and to make immunotherapy more effective for solid tumors. Indeed, when modified T lymphocytes attack it, it is harder for them than for “liquid” forms of cancer. They can therefore become less effective over time because they undergo cellular exhaustion.
“The ability to remotely activate CAR-T cells to varying degrees using different doses of an activator drug – and then deactivate them on demand, as needed – would improve the safety of this therapy, underlines Giordano Attianese, one of the authors. Additionally, remote control of CAR-T cell activity could also be used to alleviate T cell exhaustion [activés par CAR-T pour combattre les cellules tumorales] thereby improving the durability of patient responses to therapy”.
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