Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy

Weijun Wang, Nian Ling Zhu, Jason Chua, Steve Swenson, Fritz K. Costa, Stephanie Schmitmeier, Barbara A. Sosnowski, Toshiaki Shichinohe, Noriyuki Kasahara, Thomas C. Chen

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Object. Adenovirus vector (AdV)-mediated gene delivery has been recently demonstrated in clinical trials as a novel potential treatment for malignant gliomas. Combined coxsackievirus B and adenovirus receptor (CAR) has been shown to function as an attachment receptor for multiple adenovirus serotypes, whereas the vitronectin integrins (αvβ3 and αvβ5) are involved in AdV internalization. In resected glioma specimens, the authors demonstrated that malignant gliomas have varying levels of CAR, αvβ3, and αvβ5 expression. Methods. A correlation between CAR expression and the transduction efficiency of AdV carrying the green fluorescent protein in various human glioblastoma multiforme (GBM) cell lines and GBM primary cell lines was observed. To increase transgene activity in in vitro glioma cells with low or deficient levels of CAR, the authors used basic fibroblast growth factor (FGF2) as a targeting ligand to redirect adenoviral infection through its cognate receptor, FGF receptor 1 (FGFR1), which was expressed at high levels by all glioma cells. These findings were confirmed by in vivo study data demonstrating enhanced transduction efficiency of FGF2-retargeted AdV in CAR-negative intracranial gliomas compared with AdV alone, without evidence of increased angiogenesis. Conclusions. Altogether, the results demonstrated that AdV-mediated gene transfer using the FGF2/FGFR system is effective in gliomas with low or deficient levels of CAR and suggested that FGF2-retargeting of AdV may be a promising approach in glioma gene therapy.

Original languageEnglish (US)
Pages (from-to)1058-1066
Number of pages9
JournalJournal of Neurosurgery
Volume103
Issue number6
StatePublished - Dec 2005
Externally publishedYes

Fingerprint

Fibroblast Growth Factor 2
Glioma
Genetic Therapy
Adenoviridae
Ligands
Glioblastoma
Vitronectin
Fibroblast Growth Factor 1
Fibroblast Growth Factor Receptors
Cell Line
Green Fluorescent Proteins
adenovirus receptor
Transgenes
Integrins
Genes
coxsackievirus B receptor
Clinical Trials
Infection

Keywords

  • Adenoviral vector
  • Basic fibroblast growth factor
  • Gene transfer
  • Malignant glioma
  • Mouse

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Wang, W., Zhu, N. L., Chua, J., Swenson, S., Costa, F. K., Schmitmeier, S., ... Chen, T. C. (2005). Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy. Journal of Neurosurgery, 103(6), 1058-1066.

Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy. / Wang, Weijun; Zhu, Nian Ling; Chua, Jason; Swenson, Steve; Costa, Fritz K.; Schmitmeier, Stephanie; Sosnowski, Barbara A.; Shichinohe, Toshiaki; Kasahara, Noriyuki; Chen, Thomas C.

In: Journal of Neurosurgery, Vol. 103, No. 6, 12.2005, p. 1058-1066.

Research output: Contribution to journalArticle

Wang, W, Zhu, NL, Chua, J, Swenson, S, Costa, FK, Schmitmeier, S, Sosnowski, BA, Shichinohe, T, Kasahara, N & Chen, TC 2005, 'Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy', Journal of Neurosurgery, vol. 103, no. 6, pp. 1058-1066.
Wang W, Zhu NL, Chua J, Swenson S, Costa FK, Schmitmeier S et al. Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy. Journal of Neurosurgery. 2005 Dec;103(6):1058-1066.
Wang, Weijun ; Zhu, Nian Ling ; Chua, Jason ; Swenson, Steve ; Costa, Fritz K. ; Schmitmeier, Stephanie ; Sosnowski, Barbara A. ; Shichinohe, Toshiaki ; Kasahara, Noriyuki ; Chen, Thomas C. / Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy. In: Journal of Neurosurgery. 2005 ; Vol. 103, No. 6. pp. 1058-1066.
@article{b2ca0beea395451cb417aba9d7f3a3d1,
title = "Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy",
abstract = "Object. Adenovirus vector (AdV)-mediated gene delivery has been recently demonstrated in clinical trials as a novel potential treatment for malignant gliomas. Combined coxsackievirus B and adenovirus receptor (CAR) has been shown to function as an attachment receptor for multiple adenovirus serotypes, whereas the vitronectin integrins (αvβ3 and αvβ5) are involved in AdV internalization. In resected glioma specimens, the authors demonstrated that malignant gliomas have varying levels of CAR, αvβ3, and αvβ5 expression. Methods. A correlation between CAR expression and the transduction efficiency of AdV carrying the green fluorescent protein in various human glioblastoma multiforme (GBM) cell lines and GBM primary cell lines was observed. To increase transgene activity in in vitro glioma cells with low or deficient levels of CAR, the authors used basic fibroblast growth factor (FGF2) as a targeting ligand to redirect adenoviral infection through its cognate receptor, FGF receptor 1 (FGFR1), which was expressed at high levels by all glioma cells. These findings were confirmed by in vivo study data demonstrating enhanced transduction efficiency of FGF2-retargeted AdV in CAR-negative intracranial gliomas compared with AdV alone, without evidence of increased angiogenesis. Conclusions. Altogether, the results demonstrated that AdV-mediated gene transfer using the FGF2/FGFR system is effective in gliomas with low or deficient levels of CAR and suggested that FGF2-retargeting of AdV may be a promising approach in glioma gene therapy.",
keywords = "Adenoviral vector, Basic fibroblast growth factor, Gene transfer, Malignant glioma, Mouse",
author = "Weijun Wang and Zhu, {Nian Ling} and Jason Chua and Steve Swenson and Costa, {Fritz K.} and Stephanie Schmitmeier and Sosnowski, {Barbara A.} and Toshiaki Shichinohe and Noriyuki Kasahara and Chen, {Thomas C.}",
year = "2005",
month = "12",
language = "English (US)",
volume = "103",
pages = "1058--1066",
journal = "Journal of Neurosurgery",
issn = "0022-3085",
publisher = "American Association of Neurological Surgeons",
number = "6",

}

TY - JOUR

T1 - Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy

AU - Wang, Weijun

AU - Zhu, Nian Ling

AU - Chua, Jason

AU - Swenson, Steve

AU - Costa, Fritz K.

AU - Schmitmeier, Stephanie

AU - Sosnowski, Barbara A.

AU - Shichinohe, Toshiaki

AU - Kasahara, Noriyuki

AU - Chen, Thomas C.

PY - 2005/12

Y1 - 2005/12

N2 - Object. Adenovirus vector (AdV)-mediated gene delivery has been recently demonstrated in clinical trials as a novel potential treatment for malignant gliomas. Combined coxsackievirus B and adenovirus receptor (CAR) has been shown to function as an attachment receptor for multiple adenovirus serotypes, whereas the vitronectin integrins (αvβ3 and αvβ5) are involved in AdV internalization. In resected glioma specimens, the authors demonstrated that malignant gliomas have varying levels of CAR, αvβ3, and αvβ5 expression. Methods. A correlation between CAR expression and the transduction efficiency of AdV carrying the green fluorescent protein in various human glioblastoma multiforme (GBM) cell lines and GBM primary cell lines was observed. To increase transgene activity in in vitro glioma cells with low or deficient levels of CAR, the authors used basic fibroblast growth factor (FGF2) as a targeting ligand to redirect adenoviral infection through its cognate receptor, FGF receptor 1 (FGFR1), which was expressed at high levels by all glioma cells. These findings were confirmed by in vivo study data demonstrating enhanced transduction efficiency of FGF2-retargeted AdV in CAR-negative intracranial gliomas compared with AdV alone, without evidence of increased angiogenesis. Conclusions. Altogether, the results demonstrated that AdV-mediated gene transfer using the FGF2/FGFR system is effective in gliomas with low or deficient levels of CAR and suggested that FGF2-retargeting of AdV may be a promising approach in glioma gene therapy.

AB - Object. Adenovirus vector (AdV)-mediated gene delivery has been recently demonstrated in clinical trials as a novel potential treatment for malignant gliomas. Combined coxsackievirus B and adenovirus receptor (CAR) has been shown to function as an attachment receptor for multiple adenovirus serotypes, whereas the vitronectin integrins (αvβ3 and αvβ5) are involved in AdV internalization. In resected glioma specimens, the authors demonstrated that malignant gliomas have varying levels of CAR, αvβ3, and αvβ5 expression. Methods. A correlation between CAR expression and the transduction efficiency of AdV carrying the green fluorescent protein in various human glioblastoma multiforme (GBM) cell lines and GBM primary cell lines was observed. To increase transgene activity in in vitro glioma cells with low or deficient levels of CAR, the authors used basic fibroblast growth factor (FGF2) as a targeting ligand to redirect adenoviral infection through its cognate receptor, FGF receptor 1 (FGFR1), which was expressed at high levels by all glioma cells. These findings were confirmed by in vivo study data demonstrating enhanced transduction efficiency of FGF2-retargeted AdV in CAR-negative intracranial gliomas compared with AdV alone, without evidence of increased angiogenesis. Conclusions. Altogether, the results demonstrated that AdV-mediated gene transfer using the FGF2/FGFR system is effective in gliomas with low or deficient levels of CAR and suggested that FGF2-retargeting of AdV may be a promising approach in glioma gene therapy.

KW - Adenoviral vector

KW - Basic fibroblast growth factor

KW - Gene transfer

KW - Malignant glioma

KW - Mouse

UR - http://www.scopus.com/inward/record.url?scp=32044446998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32044446998&partnerID=8YFLogxK

M3 - Article

C2 - 16381193

AN - SCOPUS:32044446998

VL - 103

SP - 1058

EP - 1066

JO - Journal of Neurosurgery

JF - Journal of Neurosurgery

SN - 0022-3085

IS - 6

ER -