Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma.

Title
Publication TypeJournal Article
Year of Publication2016
AuthorsHicks MJ, Chiuchiolo MJ, Ballon D, Dyke JP, Aronowitz E, Funato K, Tabar V, Havlicek D, Fan F, Sondhi D, Kaminsky SM, Crystal RG
JournalPLoS One
Volume11
Issue10
Paginatione0162978
Date Published2016
ISSN1932-6203
KeywordsAnimals, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic, Cetuximab, Dependovirus, Gene Expression Regulation, Neoplastic, Genetic Therapy, Genetic Vectors, Glioblastoma, Humans, Male, Mice, Receptor, Epidermal Growth Factor, Survival Analysis
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.

DOI10.1371/journal.pone.0162978
Alternate JournalPLoS ONE
PubMed ID27711187
PubMed Central IDPMC5053413
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
T32 HL094284 / HL / NHLBI NIH HHS / United States