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Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice
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Tumor vasculature-targeted delivery of tumor necrosis factor-alpha

Anita Tandle1, Engy Hanna, Dominique Lorang

  • 1Tumor Angiogenesis Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Cancer
|December 18, 2008
PubMed
Abstract

Insights

This study developed a targeted gene therapy using a hybrid adeno-associated virus phage vector (AAVP) to deliver tumor necrosis factor-alpha (TNF-alpha) specifically to tumor vasculature, reducing systemic toxicity and inhibiting cancer growth.

Area of Science:

  • Oncolytic viruses
  • Gene therapy
  • Cancer research

Background:

  • Antivascular therapy is a promising cancer treatment modality.
  • Systemic delivery of tumor necrosis factor-alpha (TNF-alpha) is limited by significant toxicity and lack of antitumor activity.
  • Targeting therapeutic genes to tumor vasculature is crucial for effective and safe antivascular gene therapy.

Purpose of the Study:

  • To develop a targeted delivery system for TNF-alpha to tumor vasculature.
  • To evaluate the antitumor activity and toxicity of systemically delivered, targeted TNF-alpha.
  • To assess the potential for clinical translation of this targeted gene therapy strategy.

Main Methods:

  • A hybrid adeno-associated virus phage vector (AAVP) was engineered to target tumor endothelium and express TNF-alpha (AAVP-TNF-alpha).
  • In vitro and in vivo studies were conducted using a human melanoma tumor model.
  • The efficacy and specificity of AAVP-TNF-alpha were analyzed in melanoma xenografts in mice.

Main Results:

  • AAVP-TNF-alpha demonstrated high TNF-alpha expression in vitro.
  • Systemic administration of targeted AAVP-TNF-alpha specifically delivered the vector to tumor vasculature in vivo.
  • Targeted delivery led to TNF-alpha expression, tumor vessel apoptosis, significant tumor growth inhibition, and no observed systemic toxicity.

Conclusions:

  • Targeted AAVP vectors enable specific delivery of TNF-alpha to tumor vasculature, mitigating systemic toxicity.
  • This targeted approach holds potential for clinical translation of TNF-alpha as an antivascular cancer therapy.
  • The strategy offers a promising avenue for improving cancer treatment by enhancing efficacy and reducing side effects.

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