TRAC locus integrated anti-CD19 19(T2)28z1xx CAR-T cells

A preparation of T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19, linked to the co-stimulatory intracellular signaling domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) (CD28zeta; CD28z), and inserted into the T-cell receptor alpha constant (TRAC) locus, with potential immunostimulating and antineoplastic activities. Upon administration, the TRAC locus integrated anti-CD19 19(T2)28z1xx CAR-T cells 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 overexpressed in B-cell lineage malignancies. CD28 and CD3zeta provide co-stimulatory activity and may enhance the cytotoxic effect and anti-tumor activity of the CAR T cells. The 19(T2)28z1xx CAR includes 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. Integrating the anti-CD19 CAR to the TRAC locus may enhance both T-cell potency and the re-expression of the CAR following exposure to antigen.