title: Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma.
abstract: Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial brain tumor in adults with a mean survival of 14 to 15 months. Aberrant activation of the epidermal growth factor receptor (EGFR) plays a significant role in GBM progression, with amplification or overexpression of EGFR in 60% of GBM tumors. To target EGFR expressed by GBM, we have developed a strategy to deliver the coding sequence for cetuximab, an anti-EGFR antibody, directly to the CNS using an adeno-associated virus serotype rh.10 gene transfer vector. The data demonstrates that single, local delivery of an anti-EGFR antibody by an AAVrh.10 vector coding for cetuximab (AAVrh.10Cetmab) reduces GBM tumor growth and increases survival in xenograft mouse models of a human GBM EGFR-expressing cell line and patient-derived GBM. AAVrh10.CetMab-treated mice displayed a reduction in cachexia, a significant decrease in tumor volume and a prolonged survival following therapy. Adeno-associated-directed delivery of a gene encoding a therapeutic anti-EGFR monoclonal antibody may be an effective strategy to treat GBM.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hicks
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Chiuchiolo
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Douglas
authors.initials: D
authors.lastname: Ballon
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Dyke
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Aronowitz
authors.affiliation: Department of Neurosurgery, Memorial Sloan-Kettering Cancer Institute, New York, NY, United States of America.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Funato
authors.affiliation: Department of Neurosurgery, Memorial Sloan-Kettering Cancer Institute, New York, NY, United States of America.
authors.forename: Viviane
authors.initials: V
authors.lastname: Tabar
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Havlicek
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Fan
authors.initials: F
authors.lastname: Fan
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Dolan
authors.initials: D
authors.lastname: Sondhi
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D000068818:Cetuximab / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D000229:Dependovirus / Q000235:genetics; D066246:ErbB Receptors / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D016019:Survival Analysis
chemical_list: D066246:ErbB Receptors; D000068818:Cetuximab