NCIt definition : A preparation of autologous CD4- and CD8-positive T-lymphocytes that have been transduced
with a third-generation self-inactivating (SIN) lentiviral vector (LV) expressing
a human-derived immunoglobulin G4 (IgG4) hinge-optimized chimeric antigen receptor
(CAR) consisting of a single chain variable fragment (scFv) specific for CD19 that
is fused to a human CD28 transmembrane domain (CD28tm), the intracellular cytoplasmic
domain of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (CD3zeta), and linked
to a truncated form of the human epidermal growth factor receptor 2 (HER2tG), with
potential immunostimulating and antineoplastic activities. Upon administration, the
autologous CD4 /CD8 T-lymphocytes SCRI-huCAR19v1 specifically target and bind to
CD19-expressing neoplastic B-cells. This results in a cytotoxic T-lymphocyte (CTL)
response against CD19-expressing tumor cells and causes tumor cell lysis. CD19 is
a B-cell-specific cell surface antigen that is overexpressed in B-cell lineage tumors.
Incorporation of the costimulatory signaling domains of CD28 and 4-1BB increases human
T-cell function, expansion, and survival. Devoid of both ligand binding domains and
tyrosine kinase activity, the co-expressed HER2tG both facilitates in vivo detection
of the administered, transduced T-cells and can promote elimination of those cells
through a trastuzumab-induced antibody dependent cellular cytotoxicity (ADCC) response.;