IcasM28z

IcasM28z is a **fully human, second-generation chimeric antigen receptor (CAR) T-cell therapy** engineered to target the surface protein **mesothelin**, which is highly expressed in a majority of advanced solid tumors including malignant pleural mesothelioma, metastatic lung cancer, and metastatic breast cancer. The CAR construct contains a CD28 costimulatory domain, enhancing T-cell activation and persistence, and an **inducible caspase 9 (iCaspase-9) "suicide" safety gene**, which can be activated to eradicate the CAR T cells in the event of severe toxicity. IcasM28z is delivered regionally—primarily via intrapleural injection—for direct access to tumors in the pleural cavity. Preclinical and phase I clinical studies demonstrated anti-tumor activity, sustained CAR T-cell persistence, and a favorable safety profile, with minimal toxicity at tested doses. In some protocols, treatment is combined with checkpoint inhibitors (e.g., anti–PD-1 agents) to enhance efficacy. Development is based at Memorial Sloan Kettering Cancer Center (MSKCC), with involvement of leading investigators including Michel Sadelain and Prasad S. Adusumilli.

Other names

Mesothelin-targeted T cellsMesothelin-specific chimeric antigen receptor-positive T cellsmesothelin-targeted CAR T-cell therapy