Microgravity-cultured glioblastoma organoids integrated with microfluidic chip for CAR-γδ T evaluation
Guidong Zhu, Xiaoxue Shi, Ying Jiang, Wen Zhang, Linpei Guo, Guojing Pei, Yingchao Liu, Dongqi Tang, Chengwei Wang, Zhongzheng Sun
Abstract
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. To evaluate the efficacy of CAR-γδ T cells for GBM, this study developed the Micro-GRA&FLU platform. This low-cost, scalable platform provides a physiologically relevant model for assessing personalized immunotherapy for GBM.