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Car-T and Car-NK Therapy

CAR-T and CAR-NK therapies use engineered immune cells to recognise and attack glioblastoma cells. Early studies show potential, but tumour heterogeneity and the difficulty of sustaining an immune response remain major challenges.

Highlighted Papers

Vaja, S., Khandelwal, S., Vora, C., Khan, A. A., Wajeed, S., Sk, M. H., Baig, M. S., (2026): CAR-T/NK/M-based combination therapies in cancer: A comprehensive review. Current Problems in Cancer, Volume 61, 2026, 101269. https://doi.org/10.1016/j.currproblcancer.2026.101269

Vaja et al. review how engineered T cells, natural killer cells and macrophages may be combined with other cancer treatments. They discuss potential benefits and challenges, particularly for solid tumours; the review is not specific to glioblastoma.

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Strassheimer, F., Elleringmann, P., Ludmirski, G. et al. (2025): CAR-NK cell therapy combined with checkpoint inhibition induces an NKT cell response in glioblastoma. Br J Cancer 132, 849–860 (2025). https://doi.org/10.1038/s41416-025-02977-8

In a preclinical glioblastoma model, combining CAR-NK cells with checkpoint inhibition stimulated an NKT-cell response and strengthened antitumour activity. The findings support further research, but clinical benefit in patients has not been established

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Further Literature

  • Bagley, S.J., Desai, A.S., Fraietta, J.A. et al. (2025): Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial. Nat Med 31, 2778–2787 (2025). https://doi.org/10.1038/s41591-025-03745-0

  • Brown, C.E., Hibbard, J.C., Alizadeh, D. et al. (2024): Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial. Nat Med 30, 1001–1012 (2024). https://doi.org/10.1038/s41591-024-02875-1

  • Burger, M. C., Forster M.-T., Romanski, A., et al. (2023): Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma. Neuro-Oncology, Volume 25, Issue 11, November 2023, 2058-2071. https://doi.org/10.1093/neuonc/noad087

  • Choi, B. D., Gerstner, E. R., Frigault, M. J. et al. (2024): Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma. N Engl J Med. 2024 Apr 11;390(14):1290-1298. https://doi.org/10.1056/NEJMoa2314390

  • Li, J., Chaurasiya, S., Sun, G. et al. (2026): Developing a multimodal therapy for glioblastoma using oncolytic virus delivering CD19 and EGFRvIII antigens and bi-specific CARs . Nat Commun 17, 4839 (2026). https://doi.org/10.1038/s41467-026-71021-x

  • Li, C. H., Sharma, S., Heczey, A.A. et al. (2025): Long-term outcomes of GD2-directed CAR-T cell therapy in patients with neuroblastoma. Nat Med 31, 1125–1129 (2025). https://doi.org/10.1038/s41591-025-03513-0

  • News Article, by I. Backman, on New Research of Yale School of Medicine (2026): T Cell Therapy Shows Promise in Treating Aggressive Brain Cancer. Yale School of Medicine, August 17, 2026. https://medicine.yale.edu/news-article/t-cell-therapy-aggressive-brain-cancer/

  • Pant, K., Glassy, M. C. Editorial (2025): Current trends in immunotherapy: from monoclonal antibodies to CAR-T cells. Front Mol Med. 2025 Jun 2;5:1633469. https://doi.org/10.3389/fmmed.2025.1633469

  • Ramanathan, A., Lorimer, I.A.J. (2022): Engineered cells as glioblastoma therapeutics. Cancer Gene Ther 29, 156–166 (2022). https://doi.org/10.1038/s41417-021-00320-w

  • Savage, N., Grewal, S., Shaikh, M. V.  et al. (2026): Dual tumour-myeloid targeting of glioblastoma with GPNMB CAR-T cells. Nature. 2026 Jul 1. https://doi.org/10.1038/s41586-026-10641-1

  • Strassheimer, F., Elleringmann, P., Ludmirski, G. et al. (2025): CAR-NK cell therapy combined with checkpoint inhibition induces an NKT cell response in glioblastoma. Br J Cancer 132, 849–860 (2025). https://doi.org/10.1038/s41416-025-02977-8

  • Vaja, S., Khandelwal, S., Vora, C., Khan, A. A., Wajeed, S., Sk, M. H., Baig, M. S., (2026): CAR-T/NK/M-based combination therapies in cancer: A comprehensive review. Current Problems in Cancer, Volume 61, 2026, 101269. https://doi.org/10.1016/j.currproblcancer.2026.101269

  • Yoon, W. S., Chung, D. S. (2023): Advanced T and Natural Killer Cell Therapy for Glioblastoma. J Korean Neurosurg Soc. 2023 Jul;66(4):356-381. https://doi.org/10.3340/jkns.2022.0267

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