INTERNATIONAL CONGRESS OF
CancerGenetics
Dual-Target CAR-T Cell Strategies for Glioblastoma: Overcoming Antigen Heterogeneity and Microenvironmental Barriers
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Mousarreza Shiri,1 Mohammadreza Sharifi,2,*
1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
- Introduction: Glioblastoma (GBM) remains one of the most lethal and treatment-refractory solid tumors, largely due to its profound antigenic heterogeneity and highly immunosuppressive microenvironment. While Chimeric Antigen Receptor T-cell (CAR-T) therapy has achieved transformative success in hematologic malignancies, its translation to GBM has been limited by heterogeneous antigen expression, poor T-cell trafficking, and rapid functional exhaustion.
- Methods: Recent advances in dual-target CAR-T cell engineering such as combinatorial constructs recognizing EGFRvIII/IL13Rα2, HER2/EphA2, or GD2/B7-H3 offer promising strategies to mitigate antigen escape and enhance therapeutic durability. Moreover, the incorporation of cytokine-secreting or checkpoint-resistant designs, along with locoregional delivery approaches, has improved tumor infiltration and transient disease control in preclinical and early-phase clinical studies.
- Results: Despite these advances, challenges including T-cell persistence, on-target/off-tumor toxicity, and adaptive resistance persist
- Conclusion: This review critically examines the current landscape of dual-target CAR-T approaches in GBM, emphasizing mechanistic insights, preclinical outcomes, and translational barriers, while outlining future engineering strategies aimed at achieving sustained antitumor efficacy in this highly recalcitrant malignancy.
- Keywords: Glioblastoma; Dual-target CAR-T cells; Antigen heterogeneity; Tumor microenvironment; Immunotherapy
