autologous 19-28z/IL-18 CAR T lymphocytes

A preparation of autologous T lymphocytes engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) cluster of differentiation 19 (CD19) fused to the extracellular, transmembrane and intracellular signaling domains of the T-cell co-stimulatory receptor CD28 and the cytoplasmic signaling domain of the zeta chain of the TCR/CD3 complex (CD3-zeta) (19-28z), and expressing the human pro-inflammatory cytokine interleukin 18 (IL-18), with potential immunomodulating and antineoplastic activities. Upon intravenous administration, autologous 19-28z/IL-18 CAR T lymphocytes target, bind to, and induce selective toxicity in CD19-expressing tumor cells. IL-18 promotes T-cell persistence and potentiates the immune response against tumor cells. CD19 is a B-cell-specific cell surface antigen overexpressed in B-cell lineage tumors. Incorporation of costimulatory signaling domains increases human T-cell function, expansion, and survival.