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CD133 CAR-HL is a second-generation chimeric antigen receptor (CAR) T-cell therapy designed to target CD133 (Prominin-1), a marker for brain tumor-initiating cells (BTICs) in glioblastoma. Developed by researchers at McMaster University and the University of Toronto, the construct utilizes a humanized single-chain variable fragment (scFv) in a Heavy chain-linker-Light chain (HL) orientation. The CAR architecture includes a CD8 leader sequence, a CD8a transmembrane domain, a CD28 costimulatory domain, and a CD3ζ signaling tail. Preclinical studies demonstrate that these CAR-T cells selectively recognize and eliminate CD133-positive glioblastoma cells, which are often associated with treatment resistance and disease recurrence. The HL orientation was specifically evaluated alongside an LH orientation to optimize antigen binding and cytotoxic efficiency.
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