1. Academic Validation
  2. Microgravity-cultured glioblastoma organoids integrated with microfluidic chip for CAR-γδ T evaluation

Microgravity-cultured glioblastoma organoids integrated with microfluidic chip for CAR-γδ T evaluation

  • Commun Biol. 2025 Dec 18;8(1):1791. doi: 10.1038/s42003-025-09390-0.
Guidong Zhu 1 Xiaoxue Shi 2 Ying Jiang 3 Wen Zhang 3 Linpei Guo 3 Guojing Pei 3 Yingchao Liu 4 Dongqi Tang 5 6 Chengwei Wang 7 Zhongzheng Sun 8
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Second Qilu Hospital of Shandong University, Jinan, People's Republic of China.
  • 2 Helmeted Hornbill (Shandong) Biotechnology Co., Ltd., Jinan, People's Republic of China.
  • 3 Institute of Medical Sciences, The Second Qilu Hospital of Shandong University, Jinan, People's Republic of China.
  • 4 Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.
  • 5 Institute of Medical Sciences, The Second Qilu Hospital of Shandong University, Jinan, People's Republic of China. [email protected].
  • 6 Multidisciplinary Innovation Center for Nephrology, The Second Qilu Hospital of Shandong University, Jinan, People's Republic of China. [email protected].
  • 7 Department of Neurosurgery, The Second Qilu Hospital of Shandong University, Jinan, People's Republic of China. [email protected].
  • 8 Department of Neurosurgery, The Second Qilu Hospital of Shandong University, Jinan, People's Republic of China. [email protected].
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.

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