Title | |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Hicks MJ, Chiuchiolo MJ, Ballon D, Dyke JP, Aronowitz E, Funato K, Tabar V, Havlicek D, Fan F, Sondhi D, Kaminsky SM, Crystal RG |
Journal | PLoS One |
Volume | 11 |
Issue | 10 |
Pagination | e0162978 |
Date Published | 2016 |
ISSN | 1932-6203 |
Keywords | Animals, 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. |
DOI | 10.1371/journal.pone.0162978 |
Alternate Journal | PLoS ONE |
PubMed ID | 27711187 |
PubMed Central ID | PMC5053413 |
Grant List | P30 CA008748 / CA / NCI NIH HHS / United States T32 HL094284 / HL / NHLBI NIH HHS / United States |