Autologous T cells are genetically engineered to express a CD19-targeted chimeric antigen receptor with CD3ζ and costimulatory domains. Upon binding CD19 on malignant B cells, the CAR triggers T-cell activation, proliferation, cytokine release, and perforin/granzyme-mediated cytotoxic killing, leading to depletion of CD19+ tumor cells (and on-target depletion of normal B cells) after lymphodepletion.