Cells (Apr 2024)

A Roadmap of CAR-T-Cell Therapy in Glioblastoma: Challenges and Future Perspectives

  • Megan Montoya,
  • Marco Gallus,
  • Su Phyu,
  • Jeffrey Haegelin,
  • John de Groot,
  • Hideho Okada

DOI
https://doi.org/10.3390/cells13090726
Journal volume & issue
Vol. 13, no. 9
p. 726

Abstract

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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.

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