Suppression of intracranial human glioma growth after intramuscular administration of an adeno-associated viral vector expressing angiostatin

Hsin I. Ma, Ping Guo, Juan Li, Shinn Zong Lin, Yung Hsiao Chiang, Xiao Xiao, Shi Yuan Cheng

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Despite various therapeutic interventions, glioblastoma multiforme (GBM) is one of the most highly vascularized neoplasms in humans with poor prognosis. In this study, we show that a single i.m. injection of an adeno-associated viral (AAV) vector expressing angiostatin, a potent angiogenic inhibitor, effectively suppresses human glioma growth in the brain of nude mice. Approximately 40% of the tumor-bearing mice treated with AAV-angiostatin vector survived for >10 months (the duration of the experiments). In contrast, 100% of the tumor-bearing mice in the control groups, with or without i.m. injection of a control vector AAV-GFP, died because of excessive tumor burden by 6 weeks. High levels of angiostatin produced by the AAV vector were detected in blood circulation for >250 days after the one-time vector injection. The secreted angiostatin specifically targeted neovessels in the brain tumors, as evidenced by the diminished vessel densities and increased apoptosis of tumor cells surrounding these neovessels. Our study thus demonstrates that AAV-mediated antiangiogenesis gene therapy offers efficient and sustained systemic delivery of the therapeutic product, which in turn effectively suppresses glioma growth in the brain.

Original languageEnglish
Pages (from-to)756-763
Number of pages8
JournalCancer Research
Volume62
Issue number3
Publication statusPublished - Feb 1 2002
Externally publishedYes

Fingerprint

Angiostatins
Glioma
Growth
Injections
Neoplasms
Angiogenesis Inhibitors
Blood Circulation
Brain
Glioblastoma
Tumor Burden
Nude Mice
Brain Neoplasms
Genetic Therapy
Apoptosis
Control Groups
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Suppression of intracranial human glioma growth after intramuscular administration of an adeno-associated viral vector expressing angiostatin. / Ma, Hsin I.; Guo, Ping; Li, Juan; Lin, Shinn Zong; Chiang, Yung Hsiao; Xiao, Xiao; Cheng, Shi Yuan.

In: Cancer Research, Vol. 62, No. 3, 01.02.2002, p. 756-763.

Research output: Contribution to journalArticle

Ma, Hsin I. ; Guo, Ping ; Li, Juan ; Lin, Shinn Zong ; Chiang, Yung Hsiao ; Xiao, Xiao ; Cheng, Shi Yuan. / Suppression of intracranial human glioma growth after intramuscular administration of an adeno-associated viral vector expressing angiostatin. In: Cancer Research. 2002 ; Vol. 62, No. 3. pp. 756-763.
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