Definition

A preparation of off-the-shelf (OTS) T lymphocytes, generated from an induced pluripotent stem cell (iPSC) line, that have been genetically modified to express a CD19 1XX chimeric antigen receptor (CAR) that targets the tumor-associated antigen (TAA) CD19, linked to the co-stimulatory intracellular signaling domains of CD28 and the zeta chain of the TCR (T-cell receptor)/CD3 complex (CD3-zeta) (CD28zeta; CD28z), and inserted into the T-cell receptor alpha constant (TRAC) locus and edited for elimination of TCR expression, with potential immunostimulating and antineoplastic activities. Upon administration, the allogeneic anti-CD19 1XX-CAR T cells FT819 specifically recognize and bind to CD19-expressing tumor cells, resulting in specific T-cell-mediated tumor cell lysis. CD19 antigen is a B-cell specific cell surface antigen, which is expressed in all B-cell lineage malignancies and normal B cells. The CD19 1XX CAR T-cells include a 1928zeta mutant, 1XX, which contains one instead of all three immunoreceptor tyrosine-based activation motifs (iTAMs). This may help prevent counterproductive T-cell differentiation and exhaustion, and may enhance the anti-tumor activity of the CAR T-cells. By nullifying the TCR, the possibility of graft versus host disease (GvHD) is eliminated.