Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency.

ABSTRACT: Chimeric antigen receptors (CARs) are synthetic receptors that target and reprogram T cells to acquire augmented antitumor properties¹. CD19-specific CARs that comprise CD28 and CD3ζ signaling motifs² have induced remarkable responses in patients with refractory leukemia^3-5 and lymphoma⁶ and were recently approved by the US Food and Drug Administration⁷. These CARs program highly performing effector functions that mediate potent tumor elimination^4,8 despite the limited persistence they confer on T cells^3-6,8. Extending their functional persistence without compromising their potency should improve current CAR therapies. Strong T cell activation drives exhaustion^9,10, which may be accentuated by the redun

SUBMITTER: Feucht J 

PROVIDER: S-EPMC6532069 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature