Chimeric Antigen Receptor T Cells in Glioblastoma-Current Concepts and Promising Future
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Chimeric Antigen Receptor T Cells in Glioblastoma-Current Concepts and Promising Future. / Kringel, Rebecca; Lamszus, Katrin; Mohme, Malte.
in: CELLS-BASEL, Jahrgang 12, Nr. 13, 03.07.2023, S. 1770.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - Chimeric Antigen Receptor T Cells in Glioblastoma-Current Concepts and Promising Future
AU - Kringel, Rebecca
AU - Lamszus, Katrin
AU - Mohme, Malte
PY - 2023/7/3
Y1 - 2023/7/3
N2 - 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-13Rα2), 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.
AB - 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-13Rα2), 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.
KW - Humans
KW - Receptors, Chimeric Antigen/metabolism
KW - Glioblastoma/metabolism
KW - Receptors, Antigen, T-Cell/metabolism
KW - Neoplasm Recurrence, Local/metabolism
KW - T-Lymphocytes
KW - Tumor Microenvironment
U2 - 10.3390/cells12131770
DO - 10.3390/cells12131770
M3 - SCORING: Review article
C2 - 37443804
VL - 12
SP - 1770
JO - CELLS-BASEL
JF - CELLS-BASEL
SN - 2073-4409
IS - 13
ER -