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B-SYNC CAR T cells are an investigational cell therapy developed by researchers at the University of California, San Francisco (UCSF) for the treatment of glioblastoma. This therapy utilizes a synthetic Notch (synNotch) "prime-and-kill" circuit designed to overcome the lack of tumor-specific antigens and the heterogeneity of glioblastoma. The B-SYNC circuit uses a synNotch receptor to recognize Brevican (BCAN), a CNS-specific tissue antigen, which serves as a "priming" signal. Upon binding BCAN in the brain, the T cells are induced to express a chimeric antigen receptor (CAR) that targets EphA2 and IL-13Rα2. This localized activation strategy aims to restrict CAR expression to the central nervous system, thereby reducing off-tumor toxicity and preventing T-cell exhaustion. Preclinical data demonstrated complete tumor regression in patient-derived xenograft models and superior persistence compared to traditional CAR T cells.
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