Patient-derived tumor organoids have been leveraged for disease modeling and preclinical studies but rarely applied in real time to aid with interpretation of patient treatment responses in clinics. We recently demonstrated early efficacy signals in a first-in-human, phase 1 study of dual-targeting chimeric antigen receptor (CAR)-T cells (EGFR-IL13Rα2 CAR-T cells) in patients with recurrent glioblastoma. Here, we analyzed six sets of patient-derived glioblastoma organoids (GBOs) treated concurrently with the same autologous CAR-T cell products as patients in our phase 1 study. We found that CAR-T cell treatment led to target antigen reduction and cytolysis of tumor cells in GBOs, the degree of which correlated with CAR-T cell engraftment detected in patients’ cerebrospinal fluid (CSF). Furthermore, cytokine release patterns in GBOs mirrored those in patient CSF samples over time. Our findings highlight a unique trial design and GBOs as a valuable platform for real-time assessment of CAR-T cell bioactivity and insights into immunotherapy efficacy.

中文翻译：

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患者来源的胶质母细胞瘤类器官作为实时化身，用于评估对临床 CAR-T 细胞治疗的反应


患者来源的肿瘤类器官已被用于疾病建模和临床前研究，但很少实时应用于帮助解释临床中患者的治疗反应。我们最近在复发性胶质母细胞瘤患者中双靶向嵌合抗原受体 （CAR）-T 细胞 （EGFR-IL13Rα2 CAR-T 细胞） 的首次人体 1 期研究中证明了早期疗效信号。在这里，我们分析了六组患者来源的胶质母细胞瘤类器官 （GBO），这些类器官与我们的 1 期研究中的患者同时用相同的自体 CAR-T 细胞产品处理。我们发现 CAR-T 细胞治疗导致 GBOs 中肿瘤细胞的靶抗原减少和细胞溶解，其程度与在患者脑脊液 （CSF） 中检测到的 CAR-T 细胞植入相关。此外，随着时间的推移，GBO 中的细胞因子释放模式反映了患者 CSF 样本中的细胞因子释放模式。我们的研究结果强调了独特的试验设计和 GBO 作为实时评估 CAR-T 细胞生物活性和深入了解免疫治疗疗效的宝贵平台。