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CRISPR-edited tumor-infiltrating lymphocytes (TILs) represent an advanced form of adoptive cell therapy being developed by Herlev Hospital (National Center for Cancer Immune Therapy) for the treatment of metastatic melanoma. In this approach, TILs are isolated from a patient's tumor and subjected to CRISPR/Cas9 gene editing to knock out the *CISH* (Cytokine-Induced SH2 protein) gene. CISH is an intracellular checkpoint that negatively regulates T-cell receptor (TCR) signaling and cytokine sensitivity. By removing this brake, the modified TILs exhibit enhanced neoantigen recognition, increased proinflammatory cytokine production, and improved persistence and cytotoxic activity upon re-infusion. This therapy aims to overcome the immunosuppressive tumor microenvironment and provide more durable responses in patients who have failed standard checkpoint inhibitor therapies.
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