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PD-1-disrupted EGFRvIII-targeting CAR-T cells are an experimental cell-based immunotherapy designed for the treatment of glioblastoma multiforme (GBM). The therapy consists of T cells engineered to express a chimeric antigen receptor (CAR) that specifically targets the epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific mutation found in approximately 30% of GBM cases. To overcome the immunosuppressive tumor microenvironment and prevent T-cell exhaustion, the PD-1 (programmed cell death protein 1) gene is permanently disrupted using CRISPR/Cas9 gene-editing technology. This dual approach aims to enhance the persistence and cytolytic activity of the CAR-T cells against PD-L1-expressing glioma cells. Preclinical studies have demonstrated that these edited cells exhibit superior antitumor activity and improved survival in animal models compared to standard EGFRvIII CAR-T cells. The development is a collaborative effort involving institutions such as Massachusetts General Hospital and CRISPR Therapeutics.
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