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MSLN-CAR-T is a chimeric antigen receptor T cell (CAR-T) therapy in which patient or donor T cells are genetically engineered to express a synthetic receptor targeting mesothelin (MSLN), a tumor-associated surface glycoprotein. Mesothelin is overexpressed in many solid tumors—including ovarian, pancreatic, lung cancers, and mesothelioma—while its expression in normal tissues is limited to the mesothelium lining the pleura, peritoneum, and pericardium. The engineered T cells recognize and bind to MSLN on cancer cells via an extracellular single-chain variable fragment (scFv), leading to activation of intracellular signaling domains such as CD28 or 4-1BB co-stimulatory domains and CD3ζ chain. This triggers T-cell proliferation, cytokine secretion, cytolysis of target tumor cells, and antitumor immune responses. Various generations of MSLN-CAR constructs have been developed for improved efficacy and safety; some incorporate dual-receptor systems or affinity-tuned scFvs to enhance selectivity for tumor over normal tissue[2][5][6][7]. Preclinical studies show potent antitumor activity against solid tumors expressing high levels of MSLN[2][3][7]. Clinical trials are ongoing.
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