T lymphocytes expressing a chimeric antigen receptor (CAR) targeting the CD19 antigen (CAR. 19) may be of value for the therapy of B-cell malignancies. Because the in vivo survival, expansion and anti-lymphoma activity of CAR. 19+ T cells remain suboptimal even when the CAR contains a CD28 costimulatory endodomain, we generated a novel construct that also incorporates the interleukin-15 (IL-15) gene and an inducible caspase-9-based suicide gene (iC9/CAR. 19/IL-15). We found that compared with CAR. 19+ T cells, iC9/CAR. 19/IL-15+ T cells had:(1) greater numeric expansion upon antigen stimulation (10-fold greater expansion in vitro, and 3-to 15-fold greater expansion in vivo) and reduced cell death rate (Annexin-V+/7-AAD+ cells 10±6% for iC9/CAR. 19/IL-15+ T cells and 32±19% for CAR. 19+ T cells);(2) reduced expression of the programmed death 1 (PD-1) receptor upon antigen stimulation (PD-1+ cells< 15% for iC9/CAR. 19/IL-15+ T cells versus> 40% for CAR. 19+ T cells); and (3) improved antitumor effects in vivo (from 4.7-to 5.4-fold reduced tumor growth). In addition, iC9/CAR. 19/IL-15+ T cells were efficiently eliminated upon pharmacologic activation of the suicide gene. In summary, this strategy safely increases the anti-lymphoma/leukemia effects of CAR. 19-redirected T lymphocytes and may be a useful approach for treatment of patients with B-cell malignancies.