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Anti-mesothelin CAR-T cell therapy is an adoptive cellular immunotherapy where a patient's T cells are genetically engineered to express a chimeric antigen receptor (CAR) that recognizes mesothelin (MSLN). Mesothelin is a cell-surface glycoprotein that is highly expressed in several aggressive solid tumors, including malignant mesothelioma, pancreatic adenocarcinoma, ovarian cancer, and triple-negative breast cancer (TNBC), while maintaining low expression in normal tissues such as the pleura and peritoneum. The CAR construct typically includes an extracellular binding domain (often a single-chain variable fragment), a transmembrane domain, and intracellular signaling domains like CD3-zeta and costimulatory molecules (e.g., 4-1BB or CD28). Once infused, these cells bind to mesothelin-expressing tumor cells, leading to T-cell activation, expansion, and targeted tumor cell lysis. Research is ongoing to overcome challenges in the solid tumor microenvironment, such as immunosuppression and limited T-cell persistence, sometimes through combination strategies with nanoparticles or checkpoint inhibitors.
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