NCIt definition : 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.;