Genetically engineered T cells to target EGFRvIII expressing glioblastoma

J Neurooncol. 2009 Sep;94(3):373-82. doi: 10.1007/s11060-009-9889-1. Epub 2009 Apr 23.


Glioblastoma remains a significant therapeutic challenge, warranting further investigation of novel therapies. We describe an immunotherapeutic strategy to treat glioblastoma based on adoptive transfer of genetically modified T-lymphocytes (T cells) redirected to kill EGFRvIII expressing gliomas. We constructed a chimeric immune receptor (CIR) specific to EGFRvIII, (MR1-zeta). After in vitro selection and expansion, MR1-zeta genetically modified primary human T-cells specifically recognized EGFRvIII-positive tumor cells as demonstrated by IFN-gamma secretion and efficient tumor lysis compared to control CIRs defective in EGFRvIII binding (MRB-zeta) or signaling (MR1-delzeta). MR1-zeta expressing T cells also inhibited EGFRvIII-positive tumor growth in vivo in a xenografted mouse model. Successful targeting of EGFRvIII-positive tumors via adoptive transfer of genetically modified T cells may represent a new immunotherapy strategy with great potential for clinical applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Cancer Vaccines / genetics
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / genetics
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism*
  • Flow Cytometry / methods
  • Gene Expression / genetics
  • Glioblastoma / genetics*
  • Glioblastoma / immunology*
  • Green Fluorescent Proteins / genetics
  • Humans
  • Leukocytes, Mononuclear
  • T-Lymphocytes / immunology*
  • Transfection


  • Cancer Vaccines
  • Cytokines
  • enhanced green fluorescent protein
  • epidermal growth factor receptor VIII
  • Green Fluorescent Proteins
  • ErbB Receptors