Autologous Anti-mesothelin M28z1XXPD1DNR CAR-expressing T-cells
autologous anti-mesothelin m28z1xxpd1dnr car-expressing t-cells
A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) mesothelin (MSLN) linked to the signaling domains for the co-stimulatory molecules CD28 and CD3 zeta, as well as a PD-1 dominant negative receptor (DNR), with potential immunomodulating and antineoplastic activities. Upon administration, the autologous anti-MSLN M28z1XXPD1DNR CAR-expressing T-cells specifically target and kill MSLN-expressing tumor cells. MSLN, a cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types. PD-1, an immune checkpoint receptor expressed on T-cells, plays a key role in tumor immune evasion by binding to its ligand programmed death ligand 1 (PD-L1; cluster of differentiation 274; CD274; programmed cell death-1 ligand 1) expressed on tumor cells. PD-1 DNR lacks the PD-1 transmembrane and intracellular signaling domains and acts as a decoy receptor, thereby blocking PD-1-mediated signaling. This may decrease T-cell exhaustion and may enhance T-cell activity against MSLN-expressing tumor cells.