Summary
This excellent overview article by Maggs et al. (2021) reviews the latest CAR T cell-based approaches for the treatment of GBM. It is research-heavy and not always easy to read but provides an excellent summary of available immunotherapies, including CAR T-cell therapy, summarises the various mechanisms of CAR T-cells and their anti-tumour activity, explains challenges of treating GBMs and lists completed and continuing CAR T-cell trials.
An article in Nature summarises in simplified language two studies on CAR T-cell therapy for glioblastoma that were published in 2024.
The first study was published in Nature Medicine by Bagley and his team from the University of Pennsylvania. It reports on CAR T-cells targeting epidermal growth factor receptor (EGFR) and interleukin-13 receptor alpha 2 (IL13Ralpha2) in six patients. Tumour size reduction was observed in all patients during treatment with come neurotoxicity symptoms (side-effects) in some patients. The authors conclude that is safe to administer CAR T-cells but highlight that further research is required to demonstrate efficacy and yield longer-term results.
The second study was published in the New England Journal of Medicine by Choi and his colleagues from Massachusetts General Hospital and Harvard Medical School. The CAR T-cells administered to 3 participants with a glioblastoma target tumour cells that express either the mutated or the unmutated form of epidermal growth factor receptor (EGFR). The tumours reduced in size in all three patients but recurred in two short after treatment stopped and after six months in the third patient. Neurotoxic side-effects were acceptable.
An editorial with comments on Choi’s study and an excellent graph illustrating the process of administering CAR T-cells has been published by Jenkins and Drummond (2024). The editorial also provides a succinct summary of CAR T-cell therapy for those who prefer shorter articles.
Full text
The full text of Maggs’ review article and Jenkins’ editorial are attached below.
The Bagley and Choi articles are not freely available. It is worth reading the abstracts or just read the summary article in Nature.
Research publications
Maggs, L., Cattaneo, G., Dal, A. E., Moghaddam, A. S., & Ferrone, S. (2021). CAR T Cell-Based Immunotherapy for the Treatment of Glioblastoma. Front Neurosci, 15, 662064. https://doi.org/10.3389/fnins.2021.662064
Bagley, S. J. et al. (2024). Intrathecal bivalent CAR T cells targeting EGFR and IL13Ralpha2 in recurrent glioblastoma: phase 1 trial interim results. Nat Med. https://doi.org/10.1038/s41591-024-02893-z
Choi, B. D. et al. (2024). Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma. N Engl J Med, 390(14), 1290-1298. https://doi.org/10.1056/NEJMoa2314390
Jenkins, M. R., & Drummond, K. J. (2024). CAR T-Cell Therapy for Glioblastoma. N Engl J Med, 390(14), 1329-1332. https://doi.org/10.1056/NEJMe2401307