Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care

J Vis Exp. 2015 Feb 16:(96):52397. doi: 10.3791/52397.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Animals
  • Brain Neoplasms / immunology
  • Brain Neoplasms / therapy*
  • ErbB Receptors / genetics
  • ErbB Receptors / immunology
  • Female
  • Genetic Vectors
  • Glioblastoma / immunology
  • Glioblastoma / therapy*
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Standard of Care
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell
  • epidermal growth factor receptor VIII
  • ErbB Receptors