Chimeric Antigen Receptor T Cells in Glioblastoma-Current Concepts and Promising Future

被引:14
作者
Kringel, Rebecca [1 ]
Lamszus, Katrin [1 ]
Mohme, Malte [1 ]
机构
[1] Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, D-20246 Hamburg, Germany
关键词
CAR-T cells; immunotherapy; GBM; glioma; glioblastoma; T cells; INTRATUMORAL HETEROGENEITY; STRESS SURVEILLANCE; EFFICACY; THERAPY; INTERLEUKIN-13; TUMORS; EXPRESSION; BARRIER; SAFETY; GLIOMA;
D O I
10.3390/cells12131770
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Glioblastoma (GBM) is a highly aggressive primary brain tumor that is largely refractory to treatment and, therefore, invariably relapses. GBM patients have a median overall survival of 15 months and, given this devastating prognosis, there is a high need for therapy improvement. One of the therapeutic approaches currently tested in GBM is chimeric antigen receptor (CAR)-T cell therapy. CAR-T cells are genetically altered T cells that are redirected to eliminate tumor cells in a highly specific manner. There are several challenges to CAR-T cell therapy in solid tumors such as GBM, including restricted trafficking and penetration of tumor tissue, a highly immunosuppressive tumor microenvironment (TME), as well as heterogeneous antigen expression and antigen loss. In addition, CAR-T cells have limitations concerning safety, toxicity, and the manufacturing process. To date, CAR-T cells directed against several target antigens in GBM including interleukin-13 receptor alpha 2 (IL-13R & alpha;2), epidermal growth factor receptor variant III (EGFRvIII), human epidermal growth factor receptor 2 (HER2), and ephrin type-A receptor 2 (EphA2) have been tested in preclinical and clinical studies. These studies demonstrated that CAR-T cell therapy is a feasible option in GBM with at least transient responses and acceptable adverse effects. Further improvements in CAR-T cells regarding their efficacy, flexibility, and safety could render them a promising therapy option in GBM.
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页数:20
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