In summary, we provide comprehensive preclinical evidence of in vitro NKG2D-CAR T cell efficacy in T-ALL and AML and demonstrate that pharmacologic HDAC-inhibition achieves selective upregulation of NKG2D-ligands on the surface of AML blasts which in turn leads to enhanced NKG2D-CAR T cell efficacy. This evidence concerns the gene KLRK1 and acute lymphoblastic leukemia.