Abstract
We have utilized a recombinant adeno-associated viral (AAV) vector carrying the angiostatin gene as an anti-angiogenesis strategy to treat the malignant brain tumor in a C6 glioma/Wistar rat model. Angiostatin, as a potent angiogenesis inhibitor, shows high promises as an anti-cancer drug through the inhibition of tumor neovessel formation. However, sustained in vivo protein delivery is required to achieve the therapeutic effects. The AAV vector has been proven to be able to deliver sustained and high-level gene expression in vivo, and therefore, is well suited to such a purpose. In this study, we implanted 5 × 105 C6 glioma cells into the rat brain 7 days before gene therapy. Intratumoral injection of a high-titer AAV-angiostatin vector has rendered efficacious tumor suppression and resulted in long-term survival in 40% of the treated rats, whereas the control AAV-GFP vector did not have any therapeutic benefits. In addition, we have investigated the combined gene therapy of an adenoviral vector carrying the suicidal thymidine kinase gene along with the AAV-angiostatin vector. The combined therapy offered the best tumor-suppressive effects and increased long-term survival to 55% in the treated rats. Our study has demonstrated the potential of using AAV as a safe and effective vector for anti-angiogenic gene therapy of brain tumors.
| Original language | English |
|---|---|
| Pages (from-to) | 2-11 |
| Number of pages | 10 |
| Journal | Gene Therapy |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2002 |
| Externally published | Yes |
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Keywords
- Adeno-associated viral (AAV) vector
- Angiostatin gene
- Antiangiogenesis
- C6 glioma cells
- Gene therapy
ASJC Scopus subject areas
- Genetics
Cite this
Intratumoral gene therapy of malignant brain tumor in a rat model with angiostatin delivered by adeno-associated viral (AAV) vector. / Ma, H. I.; Lin, S. Z.; Chiang, Y. H.; Li, J.; Chen, S. L.; Tsao, Y. P.; Xiao, X.
In: Gene Therapy, Vol. 9, No. 1, 2002, p. 2-11.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intratumoral gene therapy of malignant brain tumor in a rat model with angiostatin delivered by adeno-associated viral (AAV) vector
AU - Ma, H. I.
AU - Lin, S. Z.
AU - Chiang, Y. H.
AU - Li, J.
AU - Chen, S. L.
AU - Tsao, Y. P.
AU - Xiao, X.
PY - 2002
Y1 - 2002
N2 - We have utilized a recombinant adeno-associated viral (AAV) vector carrying the angiostatin gene as an anti-angiogenesis strategy to treat the malignant brain tumor in a C6 glioma/Wistar rat model. Angiostatin, as a potent angiogenesis inhibitor, shows high promises as an anti-cancer drug through the inhibition of tumor neovessel formation. However, sustained in vivo protein delivery is required to achieve the therapeutic effects. The AAV vector has been proven to be able to deliver sustained and high-level gene expression in vivo, and therefore, is well suited to such a purpose. In this study, we implanted 5 × 105 C6 glioma cells into the rat brain 7 days before gene therapy. Intratumoral injection of a high-titer AAV-angiostatin vector has rendered efficacious tumor suppression and resulted in long-term survival in 40% of the treated rats, whereas the control AAV-GFP vector did not have any therapeutic benefits. In addition, we have investigated the combined gene therapy of an adenoviral vector carrying the suicidal thymidine kinase gene along with the AAV-angiostatin vector. The combined therapy offered the best tumor-suppressive effects and increased long-term survival to 55% in the treated rats. Our study has demonstrated the potential of using AAV as a safe and effective vector for anti-angiogenic gene therapy of brain tumors.
AB - We have utilized a recombinant adeno-associated viral (AAV) vector carrying the angiostatin gene as an anti-angiogenesis strategy to treat the malignant brain tumor in a C6 glioma/Wistar rat model. Angiostatin, as a potent angiogenesis inhibitor, shows high promises as an anti-cancer drug through the inhibition of tumor neovessel formation. However, sustained in vivo protein delivery is required to achieve the therapeutic effects. The AAV vector has been proven to be able to deliver sustained and high-level gene expression in vivo, and therefore, is well suited to such a purpose. In this study, we implanted 5 × 105 C6 glioma cells into the rat brain 7 days before gene therapy. Intratumoral injection of a high-titer AAV-angiostatin vector has rendered efficacious tumor suppression and resulted in long-term survival in 40% of the treated rats, whereas the control AAV-GFP vector did not have any therapeutic benefits. In addition, we have investigated the combined gene therapy of an adenoviral vector carrying the suicidal thymidine kinase gene along with the AAV-angiostatin vector. The combined therapy offered the best tumor-suppressive effects and increased long-term survival to 55% in the treated rats. Our study has demonstrated the potential of using AAV as a safe and effective vector for anti-angiogenic gene therapy of brain tumors.
KW - Adeno-associated viral (AAV) vector
KW - Angiostatin gene
KW - Antiangiogenesis
KW - C6 glioma cells
KW - Gene therapy
UR - http://www.scopus.com/inward/record.url?scp=0036167266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036167266&partnerID=8YFLogxK
U2 - 10.1038/sj/gt/3301616
DO - 10.1038/sj/gt/3301616
M3 - Article
C2 - 11850717
VL - 9
SP - 2
EP - 11
JO - Gene Therapy
JF - Gene Therapy
SN - 0969-7128
IS - 1
ER -