Issues

ABOUT THE COVER
Chimeric antigen receptors (CARs) are synthetic proteins in which an extracellular antigen-targeting moiety is fused to a bespoke intracellular signalling domain. The adoptive transfer of autologous CAR T-cells targeting B-cell tumor-associated antigens is now commonplace in the clinic. However, emerging evidence indicates that these receptors may sometimes signal in a tonic, ligand-independent fashion. This diagram highlights several potential strategies to prevent unintended CAR activation and thereby address the negative consequences of unconstrained tonic signalling upon CAR T-cell efficacy and persistence.