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
  • 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].
PMID: 41407922 DOI: 10.1038/s42003-025-09390-0
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.