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Updated: Jun 19, 2026
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
GD2 CAR T cells against human glioblastoma
Malvina Prapa1, Chiara Chiavelli1, Giulia Golinelli1
1Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.
Abstract:
Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma potentially opening a new therapeutic option for a still incurable cancer.
Insights
This study shows that GD2 CAR T-cell therapy effectively targets glioblastoma, a deadly brain cancer. Intracerebral injection of these CAR T-cells significantly improved survival in models, offering a promising new treatment avenue.
Area of Science:
- Oncology
- Immunotherapy
- Neuro-oncology
Background:
- Glioblastoma is an aggressive primary brain tumor with limited treatment options.
- GD2 antigen is highly expressed on patient-derived glioblastoma cells, making it a potential therapeutic target.
- Chimeric antigen receptor (CAR) T-cell therapy shows promise for solid tumors.
Purpose of the Study:
- To evaluate the efficacy of GD2-specific CAR T-cells against glioblastoma.
- To compare the effectiveness of intracerebral versus intravenous CAR T-cell delivery routes.
- To assess the safety and survival impact of GD2 CAR T-cell therapy in preclinical models.
Main Methods:
- Isolation of patient-derived glioblastoma cells with high GD2 expression.
- In vitro testing of GD2 CAR T-cell antitumor activity in 2D and 3D models.
- Orthotopic implantation of glioblastoma cells in NOD/SCID mice.
- Comparison of intracerebral and intravenous administration of GD2 CAR T-cells.
Main Results:
- GD2 CAR T-cells demonstrated robust antitumor activity in vitro and in vivo.
- Intracerebral CAR T-cell delivery significantly increased survival time in a dose-dependent manner.
- No significant side effects were observed with intracerebral CAR T-cell administration.
- TGF-β1 immunosuppression did not impede CAR T-cell antitumor activity.
Conclusions:
- Anti-GD2 CAR T-cell therapy is a potential therapeutic strategy for glioblastoma.
- Intracerebral delivery of GD2 CAR T-cells is superior to intravenous delivery for brain tumors.
- This approach offers a promising new option for treating glioblastoma.
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