A Roadmap of CAR-T-Cell Therapy in Glioblastoma: Challenges and Future Perspectives.
Megan MontoyaMarco GallusSu PhyuJeffrey HaegelinJohn de GrootHideho OkadaPublished in: Cells (2024)
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.
Keyphrases
- cell therapy
- stem cells
- mesenchymal stem cells
- randomized controlled trial
- minimally invasive
- systematic review
- blood brain barrier
- single cell
- cardiovascular events
- squamous cell carcinoma
- bone marrow
- locally advanced
- surgical site infection
- young adults
- combination therapy
- free survival
- replacement therapy
- childhood cancer