Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care |
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Authors: | Katherine Riccione Carter M Suryadevara David Snyder Xiuyu Cui John H Sampson Luis Sanchez-Perez |
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Institution: | 1.Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University;2.Department of Biomedical Engineering, Duke University;3.Department of Pathology, Duke University |
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Abstract: | Adoptive T cell immunotherapy offers a promising strategy for specifically targeting and eliminating malignant gliomas. T cells can be engineered ex vivo to express chimeric antigen receptors specific for glioma antigens (CAR T cells). The expansion and function of adoptively transferred CAR T cells can be potentiated by the lymphodepletive and tumoricidal effects of standard of care chemotherapy and radiotherapy. We describe a method for generating CAR T cells targeting EGFRvIII, a glioma-specific antigen, and evaluating their efficacy when combined with a murine model of glioblastoma standard of care. T cells are engineered by transduction with a retroviral vector containing the anti-EGFRvIII CAR gene. Tumor-bearing animals are subjected to host conditioning by a course of temozolomide and whole brain irradiation at dose regimens designed to model clinical standard of care. CAR T cells are then delivered intravenously to primed hosts. This method can be used to evaluate the antitumor efficacy of CAR T cells in the context of standard of care. |
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Keywords: | Immunology Issue 96 Tumor immunotherapy glioblastoma chimeric antigen receptor adoptive transfer temozolomide radiotherapy |
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