肿瘤细胞治疗研究
英文原题：Microgravity-cultured glioblastoma organoids integrated with microfluidic chip for CAR-γδ T evaluation.
模拟肿瘤微环境（TME）的肿瘤类器官是肿瘤免疫研究和个性化癌症治疗开发的关键工具。
模拟肿瘤微环境（TME）的肿瘤类器官是肿瘤免疫研究和个性化癌症治疗开发的关键工具。我们将微重力培养与微流控芯片技术整合（Micro-GRA& FLU），建立了一个在类生理条件下评估嵌合抗原受体（CAR）-γδ T细胞疗效的平台。患者来源的胶质母细胞瘤（GBM）细胞经微重力培养形成胶质母细胞瘤类器官（GBOs）。病理分析验证了GBOs在免疫细胞表型上与配对的GBM相似。微流控芯片评估了CAR-γδ T细胞对GBOs的细胞毒性。低成本、易操作的微重力系统生成了存活良好、均一的GBOs，并保留了GBM TME特征。CAR-γδ T细胞在微流控芯片中对GBOs表现出强细胞毒性；个体化联合治疗较单药治疗增强了其抗肿瘤活性。本研究建立了一个可扩展、具有生理相关性的Micro-GRA& FLU平台，用于在GBM类器官中评估CAR-γδ T细胞疗法。
Tumor organoids mimicking the tumor microenvironment (TME) are key tools for tumor immunity research and personalized cancer therapy development. We integrated microgravity culture with microfluidic chip technology (Micro-GRA& FLU) to establish a platform for evaluating chimeric antigen receptor (CAR)-γδ T cell efficacy under physiological-like conditions. Patient-derived glioblastoma (GBM) cells were microgravity-cultured into glioblastoma organoids (GBOs). Pathological analysis validated GBO similarity to matched GBM in immune cell phenotypes. Microfluidic chips assessed CAR-γδ T cell cytotoxicity against GBOs. The low-cost, easy-to-operate microgravity system generated viable, uniform GBOs that retained GBM TME features. CAR-γδ T cells showed strong cytotoxicity against GBOs in microfluidic chips; individualized combination therapy enhanced their antitumor activity vs. monotherapy. This study establishes a scalable, physiologically relevant Micro-GRA& FLU platform for evaluating CAR-γδ T cell therapies in GBM organoids.
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