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Updated: Jun 5, 2025
Author Spotlight: Enhanced Generation of Patient-Derived 3D Organoids for Glioblastoma and Glioma
Published on: January 19, 2024
Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy
Meghan Logun1, Xin Wang2, Yusha Sun3
1Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Abstract:
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-IL13Rα2 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.
Insights
Patient-derived tumor organoids show promise for real-time assessment of chimeric antigen receptor (CAR)-T cell therapy in glioblastoma patients. This approach correlates organoid responses with clinical outcomes, aiding immunotherapy efficacy interpretation.
Area of Science:
- Oncology
- Immunotherapy
- Biotechnology
Background:
- Patient-derived tumor organoids are valuable for preclinical research but underutilized for real-time clinical treatment response interpretation.
- Chimeric antigen receptor (CAR)-T cell therapy shows early efficacy in recurrent glioblastoma.
- Dual-targeting (EGFR-IL13Rα2) CAR-T cells are being investigated for glioblastoma treatment.
Purpose of the Study:
- To evaluate patient-derived glioblastoma organoids (GBOs) as a platform for real-time assessment of CAR-T cell therapy.
- To correlate GBO responses with clinical outcomes in patients receiving CAR-T cell therapy.
- To investigate the utility of GBOs for understanding immunotherapy bioactivity and efficacy.
Main Methods:
- Analysis of six sets of patient-derived glioblastoma organoids (GBOs).
- Concurrent treatment of GBOs with autologous CAR-T cell products used in a phase 1 clinical trial.
- Measurement of CAR-T cell-induced target antigen reduction and tumor cell cytolysis in GBOs.
- Correlation of GBO findings with CAR-T cell engraftment in patient cerebrospinal fluid (CSF) and cytokine release patterns.
Main Results:
- CAR-T cell treatment induced target antigen reduction and tumor cell cytolysis in GBOs.
- The extent of tumor cell killing in GBOs correlated with CAR-T cell engraftment detected in patient CSF.
- Cytokine release patterns observed in GBOs mirrored those found in patient CSF samples over time.
Conclusions:
- Patient-derived glioblastoma organoids serve as a valuable platform for real-time assessment of CAR-T cell bioactivity.
- GBOs can provide insights into immunotherapy efficacy by mirroring clinical responses.
- This approach offers a unique trial design for evaluating CAR-T cell therapies in glioblastoma.
