Antigen-Independent Activation Enhances The Efficacy of 4-1BB-Costimulated CD22 CAR T Cells

CD19-directed chimeric antigen receptor T-cell therapies have induced remission in patients with B-cell acute lymphoblastic leukemia (ALL), but many patients experience relapse. Two pilot clinical trials of T cells bearing a 4-1BB-based, CD22-targeting CAR in patients with relapsed or refractory ALL produced findings that suggest that tonic 4-1BB-based signaling is beneficial to CAR function and demonstrate the utility of bedside-to-bench-to-bedside translation in the design and implementation of CAR T-cell therapies.