Car-T cells therapy puts a complete halt to Car-T cell activities

Car-T cells therapy

A therapy which can transform the immune cells of a patient into cancer-killing weapons, CAR-T cell therapy, have been welcome as advancement towards the treatment of blood cancer.

However, managing the most common acute side effect associated with CAR-T cells, cytokine release syndrome is still a challenge. In Germany, a team of researchers has now discovered a likely solution in Bristol-Myers Squibb’s leukemia drug Sprycel.

Scientists at the University Hospital Würzburg revealed that Sprycel can quickly act to put a temporary pause on CAR-T cells in mice, sparing some of the animals from the potentially fatal cytokine release syndrome.

Cytokine release syndrome gets triggered when there is a release of inflammatory molecules from both innate immune cells and CAR-T cells. At present, available methods to prevent cytokine release syndrome either can’t completely control CAR-T cell function or can destroy the anti-cancer effect for good.

CAR-T therapies contain CD4+ helper T cells and CD8+ killer T cells. In laboratory dishes, it was found by researchers of the University Hospital Wurzburg that Sprycel could lock these two types of CAR-T cells in an inactive state by interfering with an enzyme called LCK, hence preventing them from the production of inflammatory molecules that cause cytokine release syndrome. According to the team, the barrier lasted for 7 days, with zero signs of the effect wearing off.

But can there be a reversal of the off switch? Sprycel was carefully removed by the researchers from the cell cultures and found that the CAR-T cells quickly switched back on & began killing target cells. Within 7 hours, CAR-T cells had regained their full power at breaking down target cells, the team reported. They showed that Sprycel could instantaneously put a complete stop to CAR-T activities, whereas dexamethasone acted comparatively slowly and demonstrated only partial inhibition.