Are We There Yet? How CAR T-Cells Came to Be and Where They'll Take Us

Abstract

  Chimeric Antigen Receptor (CAR) T-cells have shown immense promise for the treatment of blood cancers. Fundamentally, CAR T-cell therapy involves the redirection of the immune system’s natural response against pathogens towards the body’s own cancer cells. The structure of the CAR allows the circumvention of the major histocompatibility complex, thereby allowing CAR T-cells to exhibit toxicity toward a chosen antigen. Advancements in CAR structure have improved CAR T-cell expansion and potency, also giving rise to a subset of engineered T-cells that can deposit cytokines into solid tumours. However, at this time the overall scope of CAR T-cells as a therapy is limited. Solid tumours are difficult to treat with CAR T-cells due in part to lack of appropriate target antigens, physical barriers to their efficacy, and a hostile tumour microenvironment. Toxicity is also an impediment to their clinical application. In this review, the molecular and physiological basis of CAR T-cells is outlined and areas for future research are briefly explored.