Chimeric antigen receptor (CAR) T-cell therapy mediates high response rates in relapsed/refractory B-cell malignancies. 1, 2, 3, 4 However, some patients experience serious and potentially life-threatening toxicities, including cytokine release syndrome (CRS) and CAR-related encephalopathy syndrome (CRES)/neurotoxicity. 4, 5, 6, 7, 8, 9, 10, 11, 12 Tocilizumab and/or high-dose corticosteroids are usually effective at controlling CRS, but are less effective at reversing neurotoxicity. 5, 6, 7 Engineered suicide switches that induce CAR-T cell depletion 8, 9, 10 remain largely untested in the clinic, are unavailable in current commercial CAR constructs, and irreversible CAR-T cell depletion is expected to limit therapeutic efficacy. Thus, alternative approaches to modulate CAR-T cell activity in vivo that are both potent and reversible are needed. Dasatinib, a US Food and Drug Administration–approved tyrosine kinase inhibitor for the treatment of t (9; 22) chronic myelogenous leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia, suppresses T-cell activation via inhibition of proximal T-cell receptor (TCR) signaling kinases, such as Src, Fyn, and Lck. 11, 12, 13, 14 Given the similarities in the manner in which TCRs and CARs transduce intracellular signals, 15, 16 we hypothesized that dasatinib would suppress CAR-T cell activation and function.