Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 94, Issue 3, Pages 373-382Publisher
SPRINGER
DOI: 10.1007/s11060-009-9889-1
Keywords
Adoptive immunotherapy; Glioma; Chimeric immune receptor; Chimeric T cell receptor; EGFRvIII; MR1
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Funding
- Goldhirsh Foundation
- Brain Tumor Society,
- Rappaport Foundation
- NIH/NCI [CA 69246 P01]
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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-del zeta). 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.
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