The function of CAR-T therapy is to increase immune response to cancer cells by modulating inflammatory signalling and cytokine function. In up to 90% of patients undergoing CAR-T therapy, there is some degree of systemic organ dysfunction in response to excessive immune activity, termed ‘cytokine release syndrome’.
Upon infusion, the CAR-T cells migrate to malignant cells and proliferate, secreting cytokines (such as C-reactive protein, tumour necrosis factor alpha, and interleukins 2, 6 and 10) and activate other local immune cells to do the same. This positive feedback loop causes a systemic inflammatory response and results in widespread endothelial dysfunction which can be life-threatening4.
Although most patients will experience CRS in some form, the degree of severity will vary. Risk factors for CRS include higher tumour burden, concurrent infection, and type of tumour, with B-cell acute lymphoblastic leukaemia being more frequently associated with CRS5.
