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Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053413/ https://www.ncbi.nlm.nih.gov/pubmed/27711187 http://dx.doi.org/10.1371/journal.pone.0162978 |
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author | Hicks, Martin J. Chiuchiolo, Maria J. Ballon, Douglas Dyke, Jonathan P. Aronowitz, Eric Funato, Kosuke Tabar, Viviane Havlicek, David Fan, Fan Sondhi, Dolan Kaminsky, Stephen M. Crystal, Ronald G. |
author_facet | Hicks, Martin J. Chiuchiolo, Maria J. Ballon, Douglas Dyke, Jonathan P. Aronowitz, Eric Funato, Kosuke Tabar, Viviane Havlicek, David Fan, Fan Sondhi, Dolan Kaminsky, Stephen M. Crystal, Ronald G. |
author_sort | Hicks, Martin J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5053413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-50534132016-10-27 Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma Hicks, Martin J. Chiuchiolo, Maria J. Ballon, Douglas Dyke, Jonathan P. Aronowitz, Eric Funato, Kosuke Tabar, Viviane Havlicek, David Fan, Fan Sondhi, Dolan Kaminsky, Stephen M. Crystal, Ronald G. PLoS One Research Article 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. Public Library of Science 2016-10-06 /pmc/articles/PMC5053413/ /pubmed/27711187 http://dx.doi.org/10.1371/journal.pone.0162978 Text en © 2016 Hicks et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hicks, Martin J. Chiuchiolo, Maria J. Ballon, Douglas Dyke, Jonathan P. Aronowitz, Eric Funato, Kosuke Tabar, Viviane Havlicek, David Fan, Fan Sondhi, Dolan Kaminsky, Stephen M. Crystal, Ronald G. Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma |
title | Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma |
title_full | Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma |
title_fullStr | Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma |
title_full_unstemmed | Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma |
title_short | Anti-Epidermal Growth Factor Receptor Gene Therapy for Glioblastoma |
title_sort | anti-epidermal growth factor receptor gene therapy for glioblastoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053413/ https://www.ncbi.nlm.nih.gov/pubmed/27711187 http://dx.doi.org/10.1371/journal.pone.0162978 |
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