Genetically engineered T cells to target EGFRvIII expressing glioblastoma
Bullain, Szofia S.
Mulligan, Richard C.
Carter, Bob S.
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CitationBullain, Szofia S., Ayguen Sahin, Oszkar Szentirmai, Carlos Sanchez, Ning Lin, Elizabeth Baratta, Peter Waterman, Ralph Weissleder, Richard C. Mulligan, and Bob S. Carter. 2009. “Genetically Engineered T Cells to Target EGFRvIII Expressing Glioblastoma.” Journal of Neuro-Oncology 94 (3): 373–82. https://doi.org/10.1007/s11060-009-9889-1.
AbstractGlioblastoma 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41384207
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