One of the main issues with the first generation CAR-T therapies is the potentially fatal side effect cytokine release syndrome (CRS) - next-generation CAR-T therapies are being designed to avoid the issue that can impact around two-thirds of patients.
Introducing current CAR-T therapy switches on a patient's immune response - the response can be excessive, leading to an overproduction of inflammatory molecules, resulting in CRS.
CRS can lead to high fever, hypotension, hypoxia and respiratory distress. It can also lead to organ dysfunction, specifically in the liver and kidneys.
Reports suggest 50-80 per cent of current CAR-T patients experience CRS symptoms to varying degrees.
Importantly, it can be treated, but this can also stop the CAR-T therapy from working with no mechanism to turn it back on.
Yet there is hope with a major global effort underway to address the issue.
A recent publication in Science Translational Medicine suggests researchers may have identified an off-on switch for CAR-T cells - a way to prevent the potent and potentially fatal CRS using Bristol-Myers Squibb's PBS-listed leukaemia therapy SPRYCEL (dastatnib).
SPRYCEL was shown to pause CRS and the CAR-T function resumed even after seven days of 'pause' - but the research is very early, at a conceptual stage, and is yet to be proven in any human trial.