Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma.
| 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 |