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 language | English (US) |
|---|---|
| Pages (from-to) | 1058-1066 |
| Number of pages | 9 |
| Journal | Journal of Neurosurgery |
| Volume | 103 |
| Issue number | 6 |
| State | Published - Dec 2005 |
| Externally published | Yes |
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Keywords
- Adenoviral vector
- Basic fibroblast growth factor
- Gene transfer
- Malignant glioma
- Mouse
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
Cite this
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 journal › Article
}
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 -