The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells

CAR T cells that is of immediate onset and can be sustained for several days without affecting T cell viability. We show that treatment with dasatinib halts cytolytic activity, cytokine production, and proliferation of CAR T cells in vitro and in vivo. The dose of dasatinib can be titrated to achieve partial or complete inhibition of CAR T cell function. Upon discontinuation of dasatinib, the inhibitory effect is rapidly and completely reversed, and CAR T cells resume their antitumor function. The favorable pharmacodynamic attributes of dasatinib can be exploited to steer the activity of CAR T cells in "function-on-off-on" sequences in real time. In a mouse model of cytokine release syndrome (CRS), we…

• MS
  Memorial Sloan-Kettering Cancer Center
• AS
  Alexander S. Onassis Public Benefit Foundation
• DK
  Deutsche Krebshilfe

  Award: 313100
• IZ
  Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg

  Award: Z4/109 and D-244