肿瘤细胞治疗研究
英文原题：Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy.
患者来源的肿瘤类器官已被用于疾病建模和临床前研究，但很少在临床上实时应用以协助解读患者的治疗反应。
患者来源肿瘤类器官已用于疾病模型和临床前研究，但很少在临床中实时应用，以帮助解读患者治疗应答。我们近期在一项首次人体I期研究中，观察到双靶嵌合抗原受体（CAR）T细胞（EGFR-IL13Rα2 CAR-T细胞）治疗复发性胶质母细胞瘤的早期疗效信号。本研究分析了6组患者来源胶质母细胞瘤类器官（GBO），患者接受的CAR-T细胞产品与I期研究中的自体CAR-T产品相同。研究发现，CAR-T细胞治疗导致GBO中靶抗原减少并杀伤肿瘤细胞，其程度与患者脑脊液（CSF）中检测到的CAR-T细胞植入水平相关。此外，GBO中的细胞因子释放模式随时间变化，与患者CSF样本中的模式相似。本研究突显了这一独特试验设计，并表明GBO是实时评估CAR-T细胞生物活性的有价值平台，可为免疫治疗效力提供见解。
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-IL13R 2 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.
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