Mechanisms of response and resistance to CAR T cell therapies

Chimeric antigen receptor (CAR) T cell therapy is successful for some B cell malignancies but remains limited for a wider range of patients and cancers. Recent advances have shown that patients with more naïve and early memory-like T cells have better response rates due to increased expansion and persistence of the CAR T cells. The costimulatory domain used in the CAR is also important for their persistence and anti-tumor activity. Modifying these domains can improve CAR T cell efficacy. Tumors escape CAR T cell targeting through loss of the target antigen or other genetic characteristics and suppressive microenvironments. Using combinations treatments or further genetically modifying CAR T cells to overcome these limitations is the focus of current research.