autologous 1928T2z CAR T cells WZTL-002

A preparation of autologous, third-generation T lymphocytes that have been transduced with a self-inactivating lentiviral vector to express a chimeric antigen receptor (CAR) containing a single-chain variable fragment (scFv) from the monoclonal antibody FMC63, which is directed against the CD19 antigen, and linked to the co-stimulatory intracellular signaling domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) (CD28zeta; CD28z), and the Toll/interleukin-1 receptor (TIR) domain from Toll-like receptor 2 (TLR2) as an additional co-stimulatory domain, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous 1928T2z CAR T cells WZTL-002 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. In addition to CD28 and CD3zeta, the TLR2-TIR domain provides co-stimulatory activity and may enhance the cytotoxic effect and anti-tumor activity of the CAR T-cells. The TIR domain from TLR2 mediates the intracellular signaling of TLR2; TLR2 stimulation enhances T-cell activation, proliferation and cytokine production.