CAR T cell therapies for diffuse midline glioma

Bryce C Thomas; Dilana E Staudt; Alicia M Douglas; Michelle Monje; Nicholas A Vitanza; Matthew D Dun

doi:10.1016/j.trecan.2023.07.007

CAR T cell therapies for diffuse midline glioma

Trends Cancer. 2023 Oct;9(10):791-804. doi: 10.1016/j.trecan.2023.07.007. Epub 2023 Aug 3.

Authors

Bryce C Thomas¹, Dilana E Staudt¹, Alicia M Douglas¹, Michelle Monje², Nicholas A Vitanza³, Matthew D Dun⁴

Affiliations

¹ Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine, and Wellbeing, University of Newcastle, Callaghan, NSW, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.
² Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Department of Pediatrics, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA; Department of Neurosurgery, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
³ Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA.
⁴ Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine, and Wellbeing, University of Newcastle, Callaghan, NSW, Australia; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia; Paediatric Theme, Mark Hughes Foundation Centre for Brain Cancer Research, College of Health, Medicine, and Wellbeing, Callaghan, NSW, Australia. Electronic address: matt.dun@newcastle.edu.au.

PMID: 37541803
DOI: 10.1016/j.trecan.2023.07.007

Abstract

Diffuse midline glioma (DMG) is a fatal pediatric cancer of the central nervous system (CNS). The location and infiltrative nature of DMG prevents surgical resection and the benefits of palliative radiotherapy are temporary; median overall survival (OS) is 9-11 months. The tumor immune microenvironment (TIME) is 'cold', and has a dominant immunosuppressive myeloid compartment with low levels of infiltrating lymphocytes and proinflammatory molecules. Because survival statistics have been stagnant for many decades, and therapies targeting the unique biology of DMG are urgently needed, this has prompted the clinical assessment of chimeric antigen receptor (CAR) T cell therapies in this setting. We highlight the current landscape of CAR T cell therapy for DMG, the role the TIME may play in the response, and strategies to overcome treatment obstacles.

Keywords: CNS tumors; chimeric antigen receptor T cell therapy; diffuse midline glioma; locoregional infusion; tumor immune microenvironment.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Central Nervous System
Child
Glioma* / genetics
Glioma* / therapy
Humans
Immunotherapy, Adoptive*
Tumor Microenvironment