title: Genetically engineered T cells to target EGFRvIII expressing glioblastoma.
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-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-delzeta). 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.
authors.affiliation: Neurosurgical Service, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Szofia S
authors.initials: SS
authors.lastname: Bullain
authors.forename: Ayguen
authors.initials: A
authors.lastname: Sahin
authors.forename: Oszkar
authors.initials: O
authors.lastname: Szentirmai
authors.forename: Carlos
authors.initials: C
authors.lastname: Sanchez
authors.forename: Ning
authors.initials: N
authors.lastname: Lin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Baratta
authors.forename: Peter
authors.initials: P
authors.lastname: Waterman
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Richard C
authors.initials: RC
authors.lastname: Mulligan
authors.forename: Bob S
authors.initials: BS
authors.lastname: Carter
mesh_terms: D000704:Analysis of Variance; D019496:Cancer Vaccines / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; C485184:enhanced green fluorescent protein; C410723:epidermal growth factor receptor VIII; D049452:Green Fluorescent Proteins; D066246:ErbB Receptors