Extensive functional comparisons between chimeric antigen receptors and T cell receptors highlight fundamental similarities

•Compared multiple CARs to TCRs directed at the same targets in acute and long-term functional assays.•CAR-Ts similar to TCR-Ts with regard to immune modulation in vitro: cytokine (IL-2), co-stimulation (CD28), checkpoint (PD-1).•Implies commonality of signaling mechanisms for activation, proliferation, cytotoxicity.•No intrinsic advantage to either receptor class for cell therapy with respect to activation or exhaustion.