Open AccessAnti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma
Author(s) -
Martin Hicks,
Marı́a J. Chiuchiolo,
Douglas Ballon,
Jonathan P. Dyke,
Eric Aronowitz,
Kosuke Funato,
Viviane Tabar,
David F. Havlicek,
Fan Fan,
Dolan Sondhi,
Stephen M. Kaminsky,
Ronald G. Crystal
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0162978
Subject(s) - cetuximab , epidermal growth factor receptor , cancer research , genetic enhancement , epidermal growth factor , medicine , monoclonal antibody , biology , antibody , receptor , immunology , gene , biochemistry
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.