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Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans

Caroline J Breitbach1, Rozanne Arulanandam, Naomi De Silva

  • 1Jennerex Inc., 450 Sansome, San Francisco, CA 94111, USA.

Cancer Research
|February 9, 2013
PubMed

Insights

Engineered vaccinia virus JX-594 targets tumor vasculature, disrupting blood flow and causing tumor necrosis. This novel oncolytic virus shows promise for cancer treatment by selectively infecting tumor endothelial cells.

Area of Science:

  • Oncolytic virology
  • Cancer biology
  • Vascular biology

Background:

  • Targeting tumor vasculature is a key strategy in cancer therapy.
  • Previous attempts to disrupt tumor blood vessels have faced limitations.
  • The ras/MAPK signaling pathway is often activated in cancer cells.

Purpose of the Study:

  • To engineer a vaccinia virus (JX-594) to selectively target and infect tumor-associated endothelial cells.
  • To evaluate the efficacy of JX-594 in disrupting tumor vasculature and inducing tumor destruction.
  • To assess the safety and therapeutic potential of JX-594 in preclinical models and human clinical trials.

Main Methods:

  • Engineering vaccinia virus (JX-594) to target activated ras/MAPK signaling.
  • In vitro studies on human endothelial cells with VEGF or FGF-2 stimulation.
  • In vivo studies in mice involving intravenous infusion of JX-594.
  • Phase I and II clinical trials in patients with various cancer types, including hepatocellular carcinoma.

Main Results:

  • JX-594 efficiently replicated and expressed transgenes in tumor-associated endothelial cells in mice and humans.
  • Intravenous JX-594 administration led to rapid disruption of tumor blood flow, hypoxia, and necrosis in mice.
  • Clinical trials demonstrated dose-dependent endothelial cell infection and transgene expression in human tumors.
  • JX-594 treatment in hepatocellular carcinoma patients disrupted tumor perfusion without significant toxicity to normal vessels or wound healing.

Conclusions:

  • Engineered vaccinia virus JX-594 selectively targets and infects tumor-associated endothelial cells.
  • JX-594 effectively disrupts tumor vasculature, leading to tumor destruction.
  • This platform technology offers a promising approach for multifunctional oncolytic virotherapy against various cancers.

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