Nature Medicine：双靶点CAR-T细胞，有效减缓致命脑肿瘤的生长

Core Viewpoint - The article discusses a promising dual-target CAR-T cell therapy for recurrent glioblastoma (rGBM), which targets EGFR and IL13Rα2, showing potential to improve patient outcomes significantly [1][4][8]. Group 1: Background on Glioblastoma - Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, with a median survival of only 12-18 months post-diagnosis [1]. - Current treatments, including surgery, radiation, and chemotherapy, have limited effectiveness in extending survival, especially in recurrent cases where the median survival is only 6-10 months [1]. Group 2: Clinical Trial Overview - A Phase 1 clinical trial was conducted with 18 rGBM patients who underwent tumor resection followed by intrathecal delivery of dual-target CAR-T cells [4][5]. - The primary endpoints included determining dose-limiting toxicity, maximum tolerated dose, and adverse events, while secondary endpoints focused on objective imaging response, duration of response, progression-free survival, and overall survival [4]. Group 3: Results of the Clinical Trial - The maximum tolerated dose was established at 2.5×10^7 CAR-T cells, with 56% of patients experiencing grade 3 neurotoxicity, but no grade 4-5 neurotoxicity reported [5]. - Among 13 patients with measurable disease, 62% showed tumor regression post-treatment, with one patient achieving partial remission and another maintaining stable disease for over 16 months [5][6]. Group 4: Implications of Findings - The therapy demonstrated the ability to slow tumor growth in nearly two-thirds of rGBM patients, which is significant given the rapid progression typically seen in this patient population [6][7]. - Notably, some patients survived 12 months or longer post-treatment, contrasting sharply with the typical median survival of less than one year for this group [7]. - The persistence of CAR-T cells in the immune system suggests potential for long-term tumor growth prevention, with evidence of T cell infiltration and macrophage activity in tumor samples [7][8]. Group 5: Future Directions - The research team aims to refine the dual-target CAR-T cell therapy to enhance its efficacy and provide more durable responses for a broader patient population [8].