Intratumoral gene therapy of malignant brain tumor in a rat model with angiostatin delivered by adeno-associated viral (AAV) vector.

作者: HI Ma , SZ Lin , YH Chiang , J Li , SL Chen

DOI: 10.1038/SJ.GT.3301616

关键词: AdenoviridaeIn vivoGene expressionPathologyTransfectionBiologyAngiogenesis inhibitorAngiostatinGenetic enhancementCancer researchViral vector

摘要: We have utilized a recombinant adeno-associated viral (AAV) vector carrying the angiostatin gene as an anti-angiogenesis strategy to treat malignant brain tumor in C6 glioma/Wistar rat model. Angiostatin, potent angiogenesis inhibitor, shows high promises anti-cancer drug through inhibition of neovessel formation. However, sustained vivo protein delivery is required achieve therapeutic effects. The AAV has been proven be able deliver and high-level expression vivo, therefore, well suited such purpose. In this study, we implanted 5 x 10(5) glioma cells into 7 days before therapy. Intratumoral injection high-titer AAV-angiostatin rendered efficacious suppression resulted long-term survival 40% treated rats, whereas control AAV-GFP did not any benefits. addition, investigated combined therapy adenoviral suicidal thymidine kinase along with vector. offered best tumor-suppressive effects increased 55% rats. Our study demonstrated potential using safe effective for anti-angiogenic tumors.

参考文章(56)
A. L. Harris, Anti-angiogenesis Therapy and Strategies for Integrating It with Adjuvant Therapy Recent results in cancer research. ,vol. 152, pp. 341- 352 ,(1998) , 10.1007/978-3-642-45769-2_33
Josephine Tuong Nguyen, Adeno-Associated Virus and Other Potential Vectors for Angiostatin and Endostatin Gene Therapy Advances in Experimental Medicine and Biology. ,vol. 465, pp. 457- 466 ,(2002) , 10.1007/0-306-46817-4_40
Michael O'Reilly, Angiostatin: an endogenous inhibitor of angiogenesis and of tumor growth. EXS. ,vol. 79, pp. 273- 294 ,(1997)
Lynn Hlatky, Melvin E. Clouse, Ernest F. Terwilliger, Ping Wu, Josephine T. Nguyen, Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy. Cancer Research. ,vol. 58, pp. 5673- 5677 ,(1998)
Jianping Zhang, Peter McL. Black, Lorenzo Bello, Rafael Allende, Jon Strasser, Matthias Kirsch, Angiostatin suppresses malignant glioma growth in vivo Cancer Research. ,vol. 58, pp. 4654- 4659 ,(1998)
Joseph C. Glorioso, David Krisky, Peggy Marconi, Justus Cohen, David Fink, Thomas Oligino, Shusuke Moriuchi, Enhanced tumor cell killing in the presence of ganciclovir by herpes simplex virus type 1 vector-directed coexpression of human tumor necrosis factor-alpha and herpes simplex virus thymidine kinase. Cancer Research. ,vol. 58, pp. 5731- 5737 ,(1998)
Judah Folkman, Angiogenesis inhibitors generated by tumors. Molecular Medicine. ,vol. 1, pp. 120- 122 ,(1995) , 10.1007/BF03401559
R.J. Samulski, X. Zhu, X. Xiao, J.D. Brook, D.E. Housman, N. Epstein, L.A. Hunter, Targeted integration of adeno-associated virus (AAV) into human chromosome 19. The EMBO Journal. ,vol. 10, pp. 3941- 3950 ,(1991) , 10.1002/J.1460-2075.1991.TB04964.X
Tatsuhiro Joki, Marcelle Machluf, Anthony Atala, Jianhong Zhu, Nicholas T. Seyfried, Ian F. Dunn, Toshiaki Abe, Rona S. Carroll, Peter McL. Black, Continuous release of endostatin from microencapsulated engineered cells for tumor therapy. Nature Biotechnology. ,vol. 19, pp. 35- 39 ,(2001) , 10.1038/83481