M28z1XXPD1DNR

M28z1XXPD1DNR is a mesothelin-targeted CAR T-cell therapy that combines innovative design elements to enhance efficacy against solid tumors. This therapy incorporates a human mesothelin-specific single-chain variable fragment with a CD28/CD3ζ signaling domain (M28z), a modified CD3z domain (1XX), and a PD-1 dominant negative receptor (PD1DNR) that provides T-cell intrinsic checkpoint blockade. It is engineered to target mesothelin (MSLN), a protein commonly expressed in several solid tumors. Preclinical studies have shown potent antitumor activity following repeat antigen stimulation, enhanced expansion in cells equipped with the PD1DNR, ability to eradicate pleural tumors and prolong survival in mouse models, and resistance to tumor reestablishment. Early clinical testing of intrapleural administration has been well-tolerated at lowest dose levels, with no CAR T-cell related adverse events of Grade >2 or any Grade >3 adverse events reported. CAR T-cells have persisted in patients' peripheral blood for greater than four weeks and have been associated with upregulated effector cytokines.

Other names

PD-1 antibody expressing mesothelin specific CAR-T cellsPD1 antibody expressing mesothelin specific CAR-T cellsPD 1 antibody expressing mesothelin specific CAR-T cells