We describe CD123-specific CARs using chimeric scFvs derived by mixing and matching VL and VH chains of different mAbs specific for CD123, testing the activity of T cells genetically modified via the Sleeping beauty (SB) system [46–48] against AML and ALL cells as well as normal bone marrow (BM)-derived cells. This evidence concerns the gene IL3RA and acute myeloid leukemia.