Anti-epidermal growth factor receptor gene therapy for glioblastoma

Martin J. Hicks, Maria J. Chiuchiolo, Douglas Ballon, Jonathan P. Dyke, Eric Aronowitz, Kosuke Funato, Viviane Tabar, David Havlicek, Fan Fan, Dolan Sondhi, Stephen M. Kaminsky, Ronald Crystal

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere0162978
JournalPLoS One
Volume11
Issue number10
DOIs
Publication statusPublished - 1 Oct 2016
Externally publishedYes

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erbB-1 Genes
Gene therapy
gene therapy
Glioblastoma
Epidermal Growth Factor Receptor
Genetic Therapy
Tumors
neoplasms
Dependovirus
Survival
Gene transfer
genetic vectors
cachexia
therapeutics
Gene encoding
antibodies
Antibodies
Cachexia
epidermal growth factor receptors
Viruses

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hicks, M. J., Chiuchiolo, M. J., Ballon, D., Dyke, J. P., Aronowitz, E., Funato, K., ... Crystal, R. (2016). Anti-epidermal growth factor receptor gene therapy for glioblastoma. PLoS One, 11(10), [e0162978]. https://doi.org/10.1371/journal.pone.0162978

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.

In: PLoS One, Vol. 11, No. 10, e0162978, 01.10.2016.

Research output: Contribution to journalArticle

Hicks, MJ, Chiuchiolo, MJ, Ballon, D, Dyke, JP, Aronowitz, E, Funato, K, Tabar, V, Havlicek, D, Fan, F, Sondhi, D, Kaminsky, SM & Crystal, R 2016, 'Anti-epidermal growth factor receptor gene therapy for glioblastoma', PLoS One, vol. 11, no. 10, e0162978. https://doi.org/10.1371/journal.pone.0162978
Hicks MJ, Chiuchiolo MJ, Ballon D, Dyke JP, Aronowitz E, Funato K et al. Anti-epidermal growth factor receptor gene therapy for glioblastoma. PLoS One. 2016 Oct 1;11(10). e0162978. https://doi.org/10.1371/journal.pone.0162978
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. / Anti-epidermal growth factor receptor gene therapy for glioblastoma. In: PLoS One. 2016 ; Vol. 11, No. 10.
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