Cell子刊：利用蝎子毒素开发的CAR-T细胞，治疗致命脑肿瘤

Core Viewpoint - The article discusses the development of chlorotoxin (CLTX)-directed CAR-T cell therapy for recurrent glioblastoma (GBM), highlighting its feasibility and safety based on interim clinical trial data [4][8]. Group 1: Background on Glioblastoma and CAR-T Therapy - Glioblastoma (GBM) is identified as the most aggressive brain tumor, with treatment challenges stemming from phenotypic heterogeneity among patients and within tumors [6]. - Despite advancements in multimodal treatments, GBM remains highly lethal, and CAR-T cell immunotherapy is being explored as a strategy to improve patient outcomes [6]. - The overall response rate and duration of CAR-T cell therapy for GBM are still low compared to significant clinical responses observed in hematological malignancies [6]. Group 2: Chlorotoxin (CLTX) Characteristics - Chlorotoxin (CLTX) is a 36-amino acid peptide toxin derived from scorpion venom, which selectively binds to malignant glioma cells without affecting non-malignant brain cells [7]. - Previous studies have shown that CLTX can effectively guide T cells to recognize and kill glioma cells, indicating its potential for clinical application [7]. Group 3: Clinical Trial Findings - A Phase 1 clinical trial was initiated to evaluate the safety and feasibility of CLTX-CAR-T cell therapy for recurrent/refractory GBM and IDH-mutant grade IV astrocytoma patients [8]. - Interim results from the trial indicated good tolerability of the CLTX-CAR-T cell therapy, with no dose-limiting toxicities reported [8]. - Among four patients, 75% achieved stable disease as the best response, and CLTX-CAR-T cells were detected in tumor cavity effusions with low levels in the bloodstream [8]. Group 4: Future Directions - The research team plans to release a comprehensive report upon trial completion and is exploring ways to enhance the efficacy of CLTX-CAR-T cells [10]. - Potential strategies include modifications to the peptide ligand, adjustments to the CAR scaffold, and T cell engineering, as well as considering combination therapies to support the persistence and effectiveness of CLTX-CAR-T cells [10].