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Cytotoxicity and antiangiogenesis by fibroblast growth factor 2-targeted Ad-TK cancer gene therapy

Koichiro Saito1, Khurram Khan, Barbara Sosnowski

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

The Laryngoscope
|February 13, 2009
PubMed
Abstract

Insights

FGF2-targeted gene therapy using adenoviral vectors encoding herpes simplex virus thymidine kinase (Ad-TK) showed increased tumor cell death and reduced tumor volume. This novel approach also demonstrated an antiangiogenesis effect, offering a promising new treatment for FGF receptor-expressing cancers.

Area of Science:

  • Oncology
  • Gene Therapy
  • Cancer Biology

Background:

  • Fibroblast growth factor (FGF) receptors are overexpressed in various cancers, including head and neck squamous cell carcinoma (HNSCC), lung, and ovarian cancers.
  • These receptors are present on both tumor cells and the endothelial cells within the tumor microenvironment.

Purpose of the Study:

  • To investigate the efficacy of FGF2-targeted gene therapy using adenoviral vectors encoding the herpes simplex virus thymidine kinase gene (Ad-TK).
  • To determine if targeting FGF receptors can enhance transgene expression and improve antitumor responses in HNSCC.

Main Methods:

  • An Ad-TK vector conjugated with FGF2 was delivered to HNSCC xenograft tumors in nude mice.
  • Mice were treated with ganciclovir, and tumors were analyzed for HSV-tk mRNA expression, apoptosis, microvessel density, and tumor volume.

Main Results:

  • FGF2-retargeted Ad-TK gene therapy significantly increased HSV-tk mRNA expression and apoptosis.
  • A significant decrease in tumor volume and microvessel density was observed, indicating an antiangiogenesis effect.

Conclusions:

  • FGF2-retargeted Ad-TK gene therapy exhibits direct antitumor cytotoxicity and a novel antiangiogenesis effect.
  • This approach shows promise as a therapeutic strategy for cancers that express FGF receptors.

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