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Genetically engineered T cells to target EGFRvIII expressing glioblastoma

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

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.

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Acknowledgments

The work was funded by the Goldhirsh Foundation in memory of Bernie Goldhirsh, the Brain Tumor Society, the Rappaport Foundation and NIH/NCI CA 69246 P01 grant “Gene Therapy for Brain Tumors.” Dr. John Gray assisted with production of the MR1 vector.

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Authors and Affiliations

  1. Neurosurgical Service, Massachusetts General Hospital, 55 Fruit Street, Yawkey 9026, Boston, MA, 02114, USA

    Szofia S. Bullain, Ayguen Sahin, Oszkar Szentirmai, Carlos Sanchez, Ning Lin, Elizabeth Baratta & Bob S. Carter

  2. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA

    Peter Waterman & Ralph Weissleder

  3. Harvard Medical School Department of Genetics, 77 Louis Pasteur Avenue, Boston, MA, 02115, USA

    Richard C. Mulligan

Authors
  1. Szofia S. Bullain
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  2. Ayguen Sahin
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  3. Oszkar Szentirmai
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  4. Carlos Sanchez
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  5. Ning Lin
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  6. Elizabeth Baratta
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  7. Peter Waterman
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  8. Ralph Weissleder
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  9. Richard C. Mulligan
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  10. Bob S. Carter
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Corresponding author

Correspondence to Bob S. Carter.

Additional information

Szofia S. Bullain, Ayguen Sahin and Oszkar Szentirmai contributed equally.

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Bullain, S.S., Sahin, A., Szentirmai, O. et al. Genetically engineered T cells to target EGFRvIII expressing glioblastoma. J Neurooncol 94, 373–382 (2009). https://doi.org/10.1007/s11060-009-9889-1

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  • DOI: https://doi.org/10.1007/s11060-009-9889-1

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