Definition

A preparation of autologous CD4- and CD8-positive Tlymphocytes that have been transduced with a lentiviral vector (LV) expressing a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) CD19 that is fused to 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 hu man epidermal growth factor receptor 2 (HER2tG), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-CD19CAR-4-1BB/CD3zeta-HER2tG-expressing CD4+/CD8+ T lymphocytes SCRI-huCAR19v2 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 domain 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.