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**CD133 CAR-T cells with PD-1 blocking scFv** are an investigational, nonviral-engineered CAR-T-cell product designed for CD133-positive hepatocellular carcinoma. The cells express a CD133-directed CAR incorporating CD8, 4-1BB, and CD3ζ signaling elements and co-express a secreted PD-1-blocking single-chain variable fragment. The construct is generated using Sleeping Beauty transposition with minicircle DNA vectors. By recognizing CD133-positive tumor and cancer stem-like cells while locally secreting a PD-1 checkpoint-blocking scFv, the approach is intended to enhance CAR-T-cell activity and alleviate PD-1-mediated immunosuppression in the tumor microenvironment. It remains a preclinical research-stage therapy developed at Sun Yat-sen University Cancer Center, with antitumor activity reported in hepatocellular carcinoma cell-line and xenograft models.
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