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Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12

Richard J Wong1, Mei-Ki Chan, Zhenkun Yu

  • 1Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. wongr@mskcc.org

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 9, 2004
PubMed
Abstract

Insights

This study shows that an interleukin-12-expressing oncolytic herpes simplex virus (HSV) effectively treats squamous cell carcinoma (SCC) by inhibiting tumor angiogenesis. Combining HSV oncolysis with anti-angiogenic strategies offers promising clinical applications.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunology
  • Tumor angiogenesis

Background:

  • Oncolytic herpes simplex viruses (HSVs) demonstrate antitumor effects via direct cancer cell lysis.
  • HSVs can be engineered to express transgenes for enhanced therapeutic strategies.
  • Tumor angiogenesis is a critical process in cancer progression.

Purpose of the Study:

  • To investigate the efficacy of an interleukin (IL)-12-expressing HSV in treating squamous cell carcinoma (SCC).
  • To determine if IL-12 expression by HSV can inhibit tumor angiogenesis.
  • To evaluate the combined therapeutic potential of HSV oncolysis and anti-angiogenic mechanisms.

Main Methods:

  • A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042) was used.
  • NV1042, its analog (NV1023), or saline were intratumorally injected into murine SCC flank tumors.
  • Angiogenesis inhibition was assessed using in vivo Matrigel plug assays, flank tumor vascularity, and in vitro endothelial cell assays.

Main Results:

  • NV1042 treatment resulted in smaller tumor volumes compared to controls.
  • NV1042 induced significant expression of IL-12 and IFN-gamma, along with anti-angiogenic mediators.
  • Inhibition of tumor vascularity and endothelial cell tubule formation was observed with NV1042 treatment.

Conclusions:

  • IL-12 expression by oncolytic HSV enhances SCC therapy through anti-angiogenic effects.
  • Combining HSV oncolysis with angiogenesis inhibition shows potential for clinical application.
  • Further investigation into these combined strategies is warranted for cancer treatment.

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