Erschienen in:
01.09.2009 | Laboratory Investigation - Human/Animal Tissue
Genetically engineered T cells to target EGFRvIII expressing glioblastoma
verfasst von:
Szofia S. Bullain, Ayguen Sahin, Oszkar Szentirmai, Carlos Sanchez, Ning Lin, Elizabeth Baratta, Peter Waterman, Ralph Weissleder, Richard C. Mulligan, Bob S. Carter
Erschienen in:
Journal of Neuro-Oncology
|
Ausgabe 3/2009
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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.