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Trail armed oncolytic poxvirus suppresses lung cancer cell by inducing apoptosis

Jinqing Hu1, Huaiyuan Wang2, Jinfa Gu2

  • 1Laboratory of Cell Biology, Xin-yuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.

Acta Biochimica Et Biophysica Sinica
|August 24, 2018
PubMed

Insights

Engineered oncolytic poxvirus expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) enhanced lung cancer cell killing. This novel therapy demonstrated significant anti-cancer effects in vitro and in vivo lung cancer models.

Area of Science:

  • Oncolytic virology
  • Cancer gene therapy
  • Molecular oncology

Background:

  • Lung cancer presents a significant global health burden with limited therapeutic options.
  • Oncolytic virus therapy offers a promising new avenue for cancer treatment.
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates cancer cell apoptosis via death receptors.

Purpose of the Study:

  • To construct and evaluate an oncolytic poxvirus engineered to express TRAIL (Oncopox-trail) for enhanced lung cancer treatment.
  • To investigate the efficacy of Oncopox-trail in preclinical lung cancer models.
  • To determine if TRAIL expression augments the oncolytic activity of the poxvirus.

Main Methods:

  • Western blot analysis to assess death receptor expression in lung cancer cell lines.
  • In vitro cytotoxicity assays comparing Oncopox-trail with Oncopox-empty on lung cancer cells.
  • In vivo studies using human A549 and mouse Lewis lung cancer xenograft models.
  • TUNEL staining to evaluate apoptosis in tumor tissues.

Main Results:

  • Oncopox-trail exhibited superior in vitro cytotoxicity against lung cancer cells compared to the control virus.
  • TRAIL-mediated cell death was primarily through apoptosis, with minimal necrosis.
  • In vivo administration of Oncopox-trail significantly inhibited tumor growth in both human and mouse lung cancer models.
  • TUNEL staining confirmed increased apoptosis in tumors treated with Oncopox-trail.

Conclusions:

  • Engineered oncolytic poxvirus expressing TRAIL (Oncopox-trail) demonstrates potent anti-cancer activity against lung cancer.
  • TRAIL-expressing oncolytic virus represents a viable strategy to enhance therapeutic efficacy in lung cancer.
  • Further investigation into Oncopox-trail for clinical application in lung cancer is warranted.

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