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Updated: Jun 9, 2025
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Expression features of targets for anti-glioma CAR-T cell immunotherapy
Peng Zhang1,2, Chunzhao Li1,2, Yi Wang1,2
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Lu 119, Beijing, 100070, China.
Objective:
To investigate the expression features of common anti-glioma CAR-T targets (B7H3, CSPG4, EGFRv III, HER2 and IL-13Ra2) in gliomas with different grades and molecular subtypes, and explore the association of target expression with glioma malignant or immune phenotypes including immune evasion, stemness, antigen presentation, and tumor angiogenesis.
Methods:
Opal™ Multiplex immunofluorescence staining was performed on glioma tissues to detect the expression of targets, and biomarkers related to the phenotypes.
Results:
High variety of CAR-T target expression among glioma subtypes was observed. GBMs exhibited the highest expression level of all the examined targets among glioma subtypes. In all glioma cases, CSPG4 was the most prevalent target covering over 84% glioma cases, followed by B7H3 at over 64%. B7H3 exhibited the highest coverage (94%) in GBMs while CSPG4 was the most popular target in both oligodendrogliomas and astrocytomas, covering 94% and 80% cases, respectively. Bi or tri-target combination strategies markedly expanded the tumor coverage across glioma cases while increased tumor-cell coverage within tumor. PD-L1 expression was significantly enriched in all the target-positive cells (except the EGFRvIII+ cells); CD133 expression was higher in the CSPG4+ or IL-13Ra2+ cells, and CD31 elevated in the B7H3+ cells, as compared with their negative cell populations.
Conclusion:
Anti-glioma CAR-T targets have heterogenous expression and distinct tumor coverage among glioma subtypes, and closely correlate with glioma malignant or immune phenotypes.
Insights
CAR-T targets like B7H3 and CSPG4 show varied expression in gliomas. Target combinations improve coverage, correlating with malignant and immune phenotypes for better glioma treatment strategies.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Molecular Biology
Background:
- Chimeric antigen receptor T-cell (CAR-T) therapy shows promise for glioma treatment.
- Understanding the expression patterns of common anti-glioma CAR-T targets is crucial for optimizing therapeutic strategies.
- Glioma heterogeneity poses challenges for targeted therapies.
Purpose of the Study:
- To analyze the expression of B7H3, CSPG4, EGFRvIII, HER2, and IL-13Ra2 in gliomas across different grades and molecular subtypes.
- To investigate the correlation between CAR-T target expression and glioma malignant/immune phenotypes, including immune evasion, stemness, antigen presentation, and angiogenesis.
Main Methods:
- Opal™ Multiplex immunofluorescence staining was employed on glioma tissues.
- Detection of CAR-T targets and relevant phenotypic biomarkers was performed.
Main Results:
- Significant heterogeneity in CAR-T target expression was observed across glioma subtypes, with Glioblastoma Multiforme (GBM) showing the highest overall expression.
- CSPG4 was the most prevalent target (84% of cases), followed by B7H3 (64%). B7H3 was highly expressed in GBM (94%), while CSPG4 was dominant in oligodendrogliomas (94%) and astrocytomas (80%).
- Combined targeting strategies enhanced tumor coverage. PD-L1, CD133, and CD31 expression correlated with specific target-positive cells, indicating links to immune evasion and angiogenesis.
Conclusions:
- Anti-glioma CAR-T targets exhibit heterogeneous expression and distinct tumor coverage patterns among glioma subtypes.
- Target expression is closely associated with glioma malignancy and immune phenotypes, offering potential for refined therapeutic approaches.
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