Widening the therapeutic window: How tumor irradiation harnesses dendritic cells to locally amplify CAR T cells in solid tumor

Abstract

Much effort has been devoted to making chimeric antigen receptor (CAR) T cell therapy as effective in solid tumors as it has become in B cell malignancies. Although clinical trials have demonstrated that doses up to 5 × 108 CAR T cells are generally safe, these doses rarely produce durable persistence.1,2,3,4 Mesothelin- and EGFRvIII-directed CAR T cells become undetectable within weeks to months after infusion,1,2 while GD2-and HER2-directed CAR T cells persist at levels below those required to sustain effector-to-target (E:T) ratios for enduring tumor control.