Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care.
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.
Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University; Department of Biomedical Engineering, Duke University.
Katherine
K
Riccione
Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University; Department of Pathology, Duke University.
Carter M
CM
Suryadevara
Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University.
David
D
Snyder
Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University.
Xiuyu
X
Cui
Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University; Department of Biomedical Engineering, Duke University; Department of Pathology, Duke University.
John H
JH
Sampson
Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University; luis.sanchez-perez@duke.edu.
Luis
L
Sanchez-Perez
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D059039:Standard of Care; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors