Journal
IMMUNOLOGICAL REVIEWS
Volume 290, Issue 1, Pages 60-84Publisher
WILEY
DOI: 10.1111/imr.12773
Keywords
brain tumors; chimeric antigen receptors; glioblastoma; T cells
Categories
Funding
- Rising Tide Foundation
- California Institute for Regenerative Medicine [CLIN2-10248]
- Kenneth T. and Eileen L. Norris Foundation
- National Cancer Institute [1F99CA234923, 1R01CA236500]
- Meringoff Family Foundation
- Curing Kids Cancer
- Gateway for Cancer Research
- Ben and Catherine Ivy Foundation
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Malignant brain tumors, including glioblastoma, represent some of the most difficult to treat of solid tumors. Nevertheless, recent progress in immunotherapy, across a broad range of tumor types, provides hope that immunological approaches will have the potential to improve outcomes for patients with brain tumors. Chimeric antigen receptors (CAR) T cells, a promising immunotherapeutic modality, utilizes the tumor targeting specificity of any antibody or receptor ligand to redirect the cytolytic potency of T cells. The remarkable clinical response rates of CD19-targeted CAR T cells and early clinical experiences in glioblastoma demonstrating safety and evidence for disease modifying activity support the potential of further advancements ultimately providing clinical benefit for patients. The brain, however, is an immune specialized organ presenting unique and specific challenges to immune-based therapies. Remaining barriers to be overcome for achieving effective CAR T cell therapy in the central nervous system (CNS) include tumor antigenic heterogeneity, an immune-suppressive microenvironment, unique properties of the CNS that limit T cell entry, and risks of immune-based toxicities in this highly sensitive organ. This review will summarize preclinical and clinical data for CAR T cell immunotherapy in glioblastoma and other malignant brain tumors, including present obstacles to advancement.
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