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Viral vector-targeted antiangiogenic gene therapy utilizing an angiostatin complementary DNA
1Laboratory of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Research
|August 12, 1998
Summary
Gene therapy using vectors to deliver angiostatin shows promise for treating malignant gliomas. This approach inhibits tumor angiogenesis, leading to tumor cell death and growth inhibition, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Malignant gliomas have a poor prognosis despite current treatments.
- Tumor growth, especially in highly angiogenic gliomas, depends on new blood vessel formation.
- Angiostatin, a plasminogen fragment, inhibits endothelial proliferation and tumor growth.
Purpose of the Study:
- To investigate the potential of vector-mediated angiostatin gene delivery for treating malignant gliomas.
- To assess the efficacy of inhibiting tumor angiogenesis using gene therapy.
Main Methods:
- Utilized retroviral and adenoviral vectors to deliver the angiostatin cDNA.
- Evaluated the inhibition of endothelial cell growth in vitro.
- Assessed the inhibition of angiogenesis and tumor growth in vivo.
Main Results:
- Vector-mediated angiostatin gene transfer effectively inhibited endothelial cell growth in vitro.
- Inhibition of tumor-associated angiogenesis was observed in vivo.
- This led to increased apoptotic tumor cell death and suppressed tumor growth.
Conclusions:
- Vector-mediated delivery of angiostatin cDNA is a potential therapeutic strategy for malignant brain tumors.
- This approach confirms the anti-tumor activity of angiostatin and the concept of dormancy therapy.