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  • Review Article
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The development of CAR T cells for patients with CNS malignancies

Nature Reviews Clinical Oncology volume 23, pages 137–150 (2026)Cite this article

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Abstract

Chimeric antigen receptor (CAR) T cells have become standard-of-care therapies for patients with certain relapsed and/or refractory haematological malignancies over the past decade. However, this approach remains largely ineffective in patients with solid tumours, in part owing to limited CAR T cell persistence, the immunosuppressive tumour microenvironment of many solid tumours and limited trafficking of CAR T cells into tumours. Central nervous system (CNS) tumours, many of which are associated with a poor prognosis and require new treatment approaches, present additional challenges such as the presence of the blood–brain barrier as well as concerns over treatment-related neurotoxicities. Despite these difficulties, clinical trials involving both adult and paediatric patients with primary CNS tumours have provided signals of efficacy. In this Review, we discuss completed, ongoing and anticipated trials testing CAR T cells in patients with CNS tumours. We also highlight the most promising preclinical developments that might lead to novel clinical approaches in this area.

Key points

  • Advances in chimeric antigen receptor (CAR) T cell engineering, combination treatment strategies and central nervous system (CNS)-specific targeting approaches have the potential to transform the landscape of cellular immunotherapy for CNS tumours.

  • CNS tumours harbour several novel tumour-specific, and tumour-associated targets for CAR T cell approaches.

  • The immunosuppressive effects of CNS solid tumours often limit the efficacy of CAR T cells.

  • Continued interdisciplinary efforts will be crucial to translating preclinical innovations into effective clinical applications to improve the outcomes of patients with CNS malignancies.

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Fig. 1: Current and future CAR designs and targets.
Fig. 2: Future CAR T cell therapies for patients with CNS tumours.

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Authors and Affiliations

  1. Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Zev A. Binder, Stephen J. Bagley & Donald M. O’Rourke

  2. Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Zev A. Binder, Stephen J. Bagley & Donald M. O’Rourke

  3. Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Zev A. Binder & Donald M. O’Rourke

  4. Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Stephen J. Bagley

  5. Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jessica B. Foster

  6. Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Jessica B. Foster

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  1. Zev A. Binder
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  4. Donald M. O’Rourke
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Correspondence to Donald M. O’Rourke.

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Z.A.B., S.J.B. and D.M.O’R. have received research funding from Kite Pharma. J.B.F. declares no competing interests.

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Binder, Z.A., Bagley, S.J., Foster, J.B. et al. The development of CAR T cells for patients with CNS malignancies. Nat Rev Clin Oncol 23, 137–150 (2026). https://doi.org/10.1038/s41571-025-01102-1

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