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Published on: September 1, 2018
Site-Specific Considerations on Engineered T Cells for Malignant Gliomas
Nirmeen Elmadany1,2, Obada T Alhalabi3,4, Michael Platten1,2,5,6,7
1DKTK (German Cancer Consortium), Clinical Cooperation Unit (CCU), Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Abstract:
Immunotherapy has revolutionized cancer treatment. Despite the recent advances in immunotherapeutic approaches for several tumor entities, limited response has been observed in malignant gliomas, including glioblastoma (GBM). Conversely, one of the emerging immunotherapeutic modalities is chimeric antigen receptors (CAR) T cell therapy, which demonstrated promising clinical responses in other solid tumors. Current pre-clinical and interventional clinical studies suggest improved efficacy when CAR-T cells are delivered locoregionally, rather than intravenously. In this review, we summarize possible CAR-T cell administration routes including locoregional therapy, systemic administration with and without focused ultrasound, direct intra-arterial drug delivery and nanoparticle-enhanced delivery in glioma. Moreover, we discuss published as well as ongoing and planned clinical trials involving CAR-T cell therapy in malignant glioma. With increasing neoadjuvant and/or adjuvant combinatorial immunotherapeutic concepts and modalities with specific modes of action for malignant glioma, selection of administration routes becomes increasingly important.
Insights
Chimeric antigen receptor (CAR) T-cell therapy shows promise for malignant gliomas. This review explores locoregional delivery methods, aiming to improve CAR T-cell efficacy in treating brain tumors like glioblastoma.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Cellular Therapy
Background:
- Immunotherapy has transformed cancer treatment, but efficacy in malignant gliomas (e.g., glioblastoma) remains limited.
- Chimeric antigen receptor (CAR) T-cell therapy has shown significant success in other solid tumors.
- Locoregional delivery of CAR T-cells may enhance efficacy in glioma compared to systemic administration.
Purpose of the Study:
- To review and summarize various CAR T-cell administration routes for malignant glioma.
- To discuss current and planned clinical trials of CAR T-cell therapy in glioma.
- To highlight the importance of administration route selection in combinatorial immunotherapeutic strategies for glioma.
Main Methods:
- Literature review of pre-clinical and clinical studies on CAR T-cell therapy in glioma.
- Summary of administration routes: locoregional, systemic (with/without focused ultrasound), intra-arterial, and nanoparticle-enhanced delivery.
- Discussion of published, ongoing, and planned clinical trials.
Main Results:
- Limited response to current immunotherapies in malignant gliomas.
- Promising clinical responses of CAR T-cell therapy in other solid tumors.
- Pre-clinical evidence suggests improved efficacy with locoregional CAR T-cell delivery in glioma.
Conclusions:
- Optimizing CAR T-cell administration routes is crucial for improving treatment outcomes in malignant glioma.
- Further research and clinical trials are needed to establish the most effective delivery strategies.
- Combinatorial immunotherapeutic approaches require careful consideration of administration routes for enhanced efficacy.
