Publication Type	Academic Article
Authors	Hicks M, Chiuchiolo M, Ballon D, Dyke J, Aronowitz E, Funato K, Tabar V, Havlicek D, Fan F, Sondhi D, Kaminsky S, Crystal R
Journal	PLoS One
Volume	11
Issue	10
Pagination	e0162978
Date Published	10/06/2016
ISSN	1932-6203
Keywords	Cetuximab, ErbB Receptors, Genetic Therapy, 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.
DOI	10.1371/journal.pone.0162978
PubMed ID	27711187
PubMed Central ID	PMC5053413