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Updated: Aug 6, 2026
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
CAR-T cell therapy in glioblastoma: from αβ to γδ T-cell platforms
Costanza Dieli1,2,3, Roberta Costanzo4, Anna Maria Corsale1,5
1Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.
Abstract:
Glioblastoma multiforme (GBM) remains a highly aggressive brain tumor with limited treatment options and poor survival. The persistent clinical failure has driven interest in novel, immune-based strategies with higher specificity and greater cytotoxic potency, among which chimeric antigen receptor (CAR)-T-cell therapy has emerged as a leading approach. αβ CAR-T cells demonstrate safety but limited efficacy due to antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and restricted trafficking to the central nervous system (CNS). γδ CAR-T cells, combining innate major histocompatibility complex (MHC)-independent tumor recognition with engineered antigen specificity, have demonstrated preclinical cytotoxicity and features consistent with intratumoral persistence in selected models, as well as off-the-shelf potential, making them a next-generation immunotherapy strategy for GBM.
Insights
Chimeric antigen receptor (CAR)-T-cell therapy shows promise for glioblastoma multiforme (GBM). Gamma delta (γδ) CAR-T cells offer potential advantages over alpha beta (αβ) CAR-T cells for treating this aggressive brain tumor.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Cellular therapy
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis.
- Current treatments for GBM have limited efficacy.
- Novel immunotherapies, such as CAR-T-cell therapy, are being explored for GBM treatment.
Purpose of the Study:
- To evaluate the potential of gamma delta (γδ) CAR-T cells as a next-generation immunotherapy for glioblastoma multiforme (GBM).
- To compare the efficacy and mechanisms of γδ CAR-T cells with alpha beta (αβ) CAR-T cells in the context of GBM treatment.
Main Methods:
- Preclinical evaluation of γδ CAR-T cell cytotoxicity against GBM models.
- Assessment of γδ CAR-T cell features, including MHC-independent recognition and intratumoral persistence.
- Comparison of γδ CAR-T cell characteristics with αβ CAR-T cells.
Main Results:
- γδ CAR-T cells demonstrate preclinical cytotoxicity against GBM.
- γδ CAR-T cells exhibit MHC-independent tumor recognition and potential for intratumoral persistence.
- γδ CAR-T cells offer off-the-shelf potential, unlike αβ CAR-T cells.
Conclusions:
- γδ CAR-T cells represent a promising next-generation immunotherapy strategy for GBM.
- The unique properties of γδ CAR-T cells may overcome limitations associated with αβ CAR-T cells in treating GBM.
- Further research into γδ CAR-T cell therapy is warranted for GBM treatment.
