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- Title
A Roadmap of CAR-T-Cell Therapy in Glioblastoma: Challenges and Future Perspectives.
- Authors
Montoya, Megan; Gallus, Marco; Phyu, Su; Haegelin, Jeffrey; de Groot, John; Okada, Hideho
- Abstract
Glioblastoma (GBM) is the most common primary malignant brain tumor, with a median overall survival of less than 2 years and a nearly 100% mortality rate under standard therapy that consists of surgery followed by combined radiochemotherapy. Therefore, new therapeutic strategies are urgently needed. The success of chimeric antigen receptor (CAR) T cells in hematological cancers has prompted preclinical and clinical investigations into CAR-T-cell treatment for GBM. However, recent trials have not demonstrated any major success. Here, we delineate existing challenges impeding the effectiveness of CAR-T-cell therapy for GBM, encompassing the cold (immunosuppressive) microenvironment, tumor heterogeneity, T-cell exhaustion, local and systemic immunosuppression, and the immune privilege inherent to the central nervous system (CNS) parenchyma. Additionally, we deliberate on the progress made in developing next-generation CAR-T cells and novel innovative approaches, such as low-intensity pulsed focused ultrasound, aimed at surmounting current roadblocks in GBM CAR-T-cell therapy.
- Subjects
CHIMERIC antigen receptors; T cells; GLIOBLASTOMA multiforme; BRAIN tumors; T-cell exhaustion; CENTRAL nervous system
- Publication
Cells (2073-4409), 2024, Vol 13, Issue 9, p726
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells13090726