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**MSLN-CD28z CAR T cells** are chimeric antigen receptor (CAR) T cells genetically engineered to express a synthetic receptor targeting mesothelin (MSLN), a cell surface glycoprotein overexpressed in various cancers such as acute myeloid leukemia (AML), mesothelioma, pancreatic cancer, ovarian cancer, and lung cancer. The CAR incorporates a single-chain variable fragment (scFv) that binds specifically to MSLN, a CD28 costimulatory domain for T cell activation, and a CD3ζ stimulatory domain to initiate T cell cytotoxic response. These cells recognize and eliminate MSLN-positive cancer cells through direct cytotoxicity and cytokine release. They have demonstrated potent, target-specific cytotoxicity in preclinical animal models and early-phase human clinical trials, and can eradicate leukemic stem cells in AML while sparing normal hematopoietic stem and progenitor cells. Combination strategies, including inhibition of MSLN shedding or co-administration with oncolytic viruses, have been explored to enhance efficacy.
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