美国宾夕法尼亚大学Donald M. O’Rourke等研究人员合作发现，患者衍生的胶质母细胞瘤类器官可作为评估临床CAR-T细胞疗法反应的实时化身。这一研究成果于2024年12月9日在线发表在国际学术期刊《细胞—干细胞》上。

研究人员表示，患者衍生的肿瘤类器官已被用于疾病建模和临床前研究，但在临床中实时应用以帮助解读患者治疗反应的情况较少。研究人员最近在一项首例人体临床1期研究中，展示了针对复发性胶质母细胞瘤的双靶向嵌合抗原受体（CAR）T细胞（EGFR-IL13Rα2 CAR-T细胞）的早期疗效信号。

研究人员分析了六组患者衍生的胶质母细胞瘤类器官（GBO），这些类器官与其1期研究中的患者接受相同的自体CAR-T细胞治疗。研究人员发现，CAR-T细胞治疗导致了GBO中靶抗原的减少和肿瘤细胞的溶解，其程度与患者脑脊液（CSF）中检测到的CAR-T细胞植入量相关。

此外，GBO中的细胞因子释放模式与患者CSF样本中的模式随时间变化呈一致性。这些研究结果突显了一种独特的试验设计，并将GBO作为实时评估CAR-T细胞生物活性和洞察免疫疗法疗效的宝贵平台。

附：英文原文

Title: Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy

Author: Meghan Logun, Xin Wang, Yusha Sun, Stephen J. Bagley, Nannan Li, Arati Desai, Daniel Y. Zhang, MacLean P. Nasrallah, Emily Ling-Lin Pai, Bike Su Oner, Gabriela Plesa, Donald Siegel, Zev A. Binder, Guo-li Ming, Hongjun Song, Donald M. O’Rourke

Issue&Volume: 2024-12-09

Abstract: 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.

DOI: 10.1016/j.stem.2024.11.010

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00409-0