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CAR-CLTX extracellular vesicles (EXTH-145) are a novel therapeutic modality consisting of extracellular vesicles (EVs) derived from neutrophils that have been engineered to express a chimeric antigen receptor (CAR) incorporating chlorotoxin (CLTX). These EVs are produced by differentiating induced pluripotent stem cells (iPSCs) into neutrophils after inserting CAR-CLTX DNA into a safe harbor locus. The resulting EVs retain the tumor-targeting capabilities of the parent CAR-neutrophils, specifically targeting glioblastoma cells via the CLTX domain. In addition to direct CAR-mediated targeting, these EVs carry a cargo of anti-tumor proteins and tumor-suppressive microRNAs (such as miR-182) that induce apoptosis and modulate various signaling pathways, including Jak-STAT, Hedgehog, and NK cell-mediated cytotoxicity. This approach aims to provide the therapeutic benefits of CAR-neutrophils while minimizing the systemic off-target effects associated with whole-cell administration.
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