NCIt definition : A preparation of autologous T-lymphocytes engineered to express a tri-functional chimeric
antigen receptor (CAR) specific for the tumor-associated antigen (TAA) cluster of
differentiation 19 (CD19), and an extracellular domain consisting of interleukin 15
(IL-15) and programmed cell death 1 (PD1; PDCD1; CD279; programmed death-1), linked
to the intracellular signaling domains of 4-1BB (CD137) and the zeta chain of the
TCR/CD3 complex (TCRzeta; CD247; CD3zeta), with potential antineoplastic activity.
Upon intravenous administration, autologous anti-CD19CAR-CD3zeta-4-1BB-IL-15-PD1-expressing
tri-functional T-lymphocytes target, bind to, and induce selective toxicity in CD19-expressing
tumor cells. IL-15 is a pro-survival cytokine that promotes T-cell persistence and
potentiates the immune response against tumor cells. The PD1 moiety binds to programmed
cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) on tumor cells,
reversing T-cell inactivation caused by endogenous PD1/PD-L1 signaling and enhancing
the cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing
tumor cells. CD19 is a B-cell-specific cell surface antigen overexpressed in B-cell
lineage tumors. Incorporation of the costimulatory signaling domains increases human
T-cell function, expansion, and survival.;