BRAIN AND NERVOUS SYSTEM: Edited by Marc Sanson and Anna-Luisa Di StefanoFuture development of chimeric antigen receptor T cell therapies for patients suffering from malignant gliomaWatchmaker, Payal B.a; Colton, Maggiea; Pineo-Cavanaugh, Psalm L.a; Okada, Hidehoa,b Author Information aDepartment of Neurosurgery, University of California, San Francisco bParker Institute for Cancer Immunotherapy, San Francisco, California, USA Correspondence to Hideho Okada, MD, PhD, Neurological Surgery, University of California San Francisco, Member, Parker Institute for Cancer Immunotherapy, Helen Diller Family Cancer Research Building HD 472 (UCSF Box 0520), 1450 3rd Street, San Francisco, CA 94158, USA. Tel: +1 415 476 1637; e-mail: [email protected] Current Opinion in Oncology 34(6):p 661-669, November 2022. | DOI: 10.1097/CCO.0000000000000877 Buy Metrics Abstract Purpose of review Chimeric antigen receptor (CAR) T cell therapy has been successful in some haematologic malignancies, but the central nervous system (CNS) presents unique obstacles to its use against tumours arising therein. This review discusses recent improvements in the delivery and design of these cells to improve the efficacy and safety of this treatment against malignant gliomas. Recent findings The immunosuppressive environment of the CNS affects the functionality of CAR T cells, but recent developments using metabolic manipulation and cytokine delivery have shown that the performance of CAR T cells can be improved in this environment. Emerging techniques can improve the delivery of CAR T cells to the CNS parenchyma, which is normally well protected from peripheral immune cells. The implementation of novel antigens and CAR-expression regulation strategies will improve the specificity and efficacy of these cells. Finally, although autologous T cells have historically been the standard, recent developments have made the use of allogeneic T cells or natural killer (NK) cells more clinically feasible. Summary The discoveries highlighted in this review will aid the development of CAR cells that are safer, more resilient against immunosuppressive signals in the CNS, and able to specifically target intracranial tumour cells. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.