Journal of Neuro-Oncology

, Volume 94, Issue 3, pp 373–382

Genetically engineered T cells to target EGFRvIII expressing glioblastoma

  • Szofia S. Bullain
  • Ayguen Sahin
  • Oszkar Szentirmai
  • Carlos Sanchez
  • Ning Lin
  • Elizabeth Baratta
  • Peter Waterman
  • Ralph Weissleder
  • Richard C. Mulligan
  • Bob S. Carter
Laboratory Investigation - Human/Animal Tissue

Abstract

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-ζ). After in vitro selection and expansion, MR1-ζ genetically modified primary human T-cells specifically recognized EGFRvIII-positive tumor cells as demonstrated by IFN-γ secretion and efficient tumor lysis compared to control CIRs defective in EGFRvIII binding (MRB-ζ) or signaling (MR1-delζ). MR1-ζ 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.

Keywords

Adoptive immunotherapy Glioma Chimeric immune receptor Chimeric T cell receptor EGFRvIII MR1 

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Szofia S. Bullain
    • 1
  • Ayguen Sahin
    • 1
  • Oszkar Szentirmai
    • 1
  • Carlos Sanchez
    • 1
  • Ning Lin
    • 1
  • Elizabeth Baratta
    • 1
  • Peter Waterman
    • 2
  • Ralph Weissleder
    • 2
  • Richard C. Mulligan
    • 3
  • Bob S. Carter
    • 1
  1. 1.Neurosurgical Service, Massachusetts General HospitalBostonUSA
  2. 2.Center for Systems BiologyMassachusetts General HospitalBostonUSA
  3. 3.Harvard Medical School Department of GeneticsBostonUSA

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