Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy

Josephine T. Nguyen, Ping Wu, Melvin E. Clouse, Lynn Hlatky, Ernest F. Terwilliger

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Antiangiogenic tumor therapies have recently attracted intense interest for their broad-spectrum action, low toxicity, and, in the case of direct endothelial targeting, an absence of drug resistance. To promote tumor regression and to maintain dormancy, antiangiogenic agents need to be chronically administered. Gene therapy offers a potential way to achieve sustained therapeutic release of potent antiangiogenic substances. As a step toward this goal, we have generated recombinant adeno-associated virus (rAAV) vectors that carry genes coding for angiostatin, endostatin, and an antisense mRNA species against vascular endothelial growth factor (VEGF). These rAAVs efficiently transduced three human tumor cell lines tested. Transduction with an rAAV-encoding antisense VEGF mRNA inhibited the production of endogenous tumor cell VEGF. Conditioned media from cells transduced with this rAAV or with rAAV-expressing endostatin or angiostatin inhibited capillary endothelial cell proliferation in vitro. Antiangiogenic rAAVs may offer a novel gene therapy approach to undermining tumor neovascularization and cancer progression.

Original languageEnglish (US)
Pages (from-to)5673-5677
Number of pages5
JournalCancer Research
Volume58
Issue number24
StatePublished - Dec 15 1998
Externally publishedYes

Fingerprint

Dependovirus
Angiostatins
Endostatins
Vascular Endothelial Growth Factor A
Neoplasms
Genetic Therapy
Messenger RNA
Angiogenesis Inhibitors
Conditioned Culture Medium
Tumor Cell Line
Drug Resistance
Endothelial Cells
Cell Proliferation
Therapeutics
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nguyen, J. T., Wu, P., Clouse, M. E., Hlatky, L., & Terwilliger, E. F. (1998). Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy. Cancer Research, 58(24), 5673-5677.

Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy. / Nguyen, Josephine T.; Wu, Ping; Clouse, Melvin E.; Hlatky, Lynn; Terwilliger, Ernest F.

In: Cancer Research, Vol. 58, No. 24, 15.12.1998, p. 5673-5677.

Research output: Contribution to journalArticle

Nguyen, JT, Wu, P, Clouse, ME, Hlatky, L & Terwilliger, EF 1998, 'Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy', Cancer Research, vol. 58, no. 24, pp. 5673-5677.
Nguyen JT, Wu P, Clouse ME, Hlatky L, Terwilliger EF. Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy. Cancer Research. 1998 Dec 15;58(24):5673-5677.
Nguyen, Josephine T. ; Wu, Ping ; Clouse, Melvin E. ; Hlatky, Lynn ; Terwilliger, Ernest F. / Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy. In: Cancer Research. 1998 ; Vol. 58, No. 24. pp. 5673-5677.
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