Progress in the development of cytokine armoured CAR T cells

The engineering of chimeric antigen receptor (CAR) T cells has evolved from first-generation constructs to sophisticated armoured CAR T cells of the fourth generation. These advanced cellular constructs are engineered to co-express cytokines, chemokines or other immunomodulatory factors alongside CARs, aiming to enhance the efficacy, safety and persistence of CAR T cells within the tumour microenvironment. In particular, the potential for reversion of immunosuppression may allow for the treatment of solid tumours, which are in need of new therapeutic options. Here, we explore clinical and preclinical findings with cytokine-enhanced CAR T cells and discuss strategies for conditional cytokine secretion to mitigate systemic toxicity.