2019
DOI: 10.1111/imr.12773
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CAR T cells for brain tumors: Lessons learned and road ahead

Abstract: 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 ce… Show more

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Cited by 173 publications
(170 citation statements)
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References 267 publications
(533 reference statements)
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“…In this context, it is hypothesised that targeting PD1 may reverse the immunosuppressive TME, causing increased CAR-T-cell efficacy. 71 IL-13 receptor alpha 2 (IL13Ra2) represents another promising tumour-associated antigen target to reverse the immunosuppressive TME via CAR-T-cell technology. 72 This high affinity IL13 receptor is significantly upregulated in mesenchymal GBM compared with normal tissue.…”
Section: Chimeric Antigen Receptor-t-cell Therapymentioning
confidence: 99%
See 1 more Smart Citation
“…In this context, it is hypothesised that targeting PD1 may reverse the immunosuppressive TME, causing increased CAR-T-cell efficacy. 71 IL-13 receptor alpha 2 (IL13Ra2) represents another promising tumour-associated antigen target to reverse the immunosuppressive TME via CAR-T-cell technology. 72 This high affinity IL13 receptor is significantly upregulated in mesenchymal GBM compared with normal tissue.…”
Section: Chimeric Antigen Receptor-t-cell Therapymentioning
confidence: 99%
“…72 This high affinity IL13 receptor is significantly upregulated in mesenchymal GBM compared with normal tissue. 71 Initial studies have successfully delivered CAR-T cells targeting IL13Ra2 intracranially. While an antitumour response has been elicited in a subset of patients, a survival benefit could not be established, given the limited number of patients (n ¼ 3).…”
Section: Chimeric Antigen Receptor-t-cell Therapymentioning
confidence: 99%
“…The translational relevance of this study also raises questions for further investigation. Neurological toxicities, collectively referred to as CAR T cell-related encephalopathy syndrome, occur in approximately 12% to 32% of patients treated with CD19 CARs, highlighting the life-threatening risks of immune inflammatory reactions in the central nervous system (8,9). Additionally, high-dose intravenous infusion (1 × 10 10 T cells) increases the risk of serious pulmonary toxicities (10).…”
Section: Discussionmentioning
confidence: 99%
“…Afterwards, engineered T-cells are amplified in a special medium that supports cell-growth. Lastly, the T-cells are injected back into the patient [159]. In glioblastoma, CAR-T against antigen IL13Rα2, human epidermal growth factor receptor 2 (HER2), and EGFRvIII have been developed [160].…”
Section: Chimeric Antigen Receptor T-cellsmentioning
confidence: 99%
“…IL13Rα2 is a high affinity IL-13 receptor that is overexpressed in glioblastoma, including glioblastoma stem cells, and it is related to poor survival [159]. Its expression is associated with the mesenchymal subtype of glioblastomas, which is also characterized by its proinflammatory nature.…”
Section: Chimeric Antigen Receptor T-cellsmentioning
confidence: 99%