Development of lentiviral vectors for antiangiogenic gene delivery. Academic Article uri icon

Overview

abstract

  • Growth and metastasis of malignant tumors requires angiogenesis. Inhibition of tumor-induced angiogenesis may represent an effective cytostatic strategy. We have constructed recombinant self-inactivating lentiviral vectors expressing angiostatin and endostatin, and have tested their antiangiogenic activities. As VSV-G-pseudotyped lentiviral vectors showed low relative transduction titers on bovine aortic and human umbilical vein endothelial cells, it was difficult to achieve significant inhibition of endothelial cell growth by lentivirus-mediated antiangiogenic gene transfer directly to endothelial cells without concomitant vector-associated cytotoxicity. However, lentivirus vectors could efficiently and stably transduce T24 human bladder cancer cells that are relatively resistant to adenovirus infection due to loss of coxsackievirus-adenovirus receptor expression. Long-term expression and secretion of angiostatin and endostatin from lentivirus-transduced T24 cells resulted in significant inhibition of cellular proliferation on coculture with endothelial cells. This report represents the first use of lentivirus-based vectors to deliver the antiangiogenic factors, angiostatin and endostatin, and suggests the potential utility of antiangiogenic gene therapy with lentiviral vectors for the treatment of cancer.

publication date

  • November 1, 2001

Research

keywords

  • Angiogenesis Inhibitors
  • Collagen
  • Genetic Vectors
  • Lentivirus
  • Peptide Fragments
  • Plasminogen

Identity

Scopus Document Identifier

  • 0035190393

Digital Object Identifier (DOI)

  • 10.1038/sj.cgt.7700388

PubMed ID

  • 11773978

Additional Document Info

volume

  • 8

issue

  • 11