Self‑complementary adeno‑associated virus 5‑mediated gene transduction of a novel CD40L mutant confers direct antitumor effects in lung carcinoma

  • Authors:
    • Wei Xu
    • Yuanyuan Xu
    • Yunyan Wei
    • Yaoxi Tan
    • Hongye Zhao
    • Weihong Zhao
    • Jianqing Wu
  • View Affiliations

  • Published online on: October 24, 2014     https://doi.org/10.3892/mmr.2014.2765
  • Pages: 482-488
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Abstract

CD40 ligand (CD40L) gene therapy offers a potentially useful option for lung cancer due to its multiple antitumor activities. However, membrane‑bound CD40L may be proteolytically cleaved to form soluble CD40L (sCD40L), which results in adverse effects. In a previous study by our group, it was demonstrated that recombinant self‑complementary adeno‑associated virus 5 (scAAV5) efficiently delivered genes to lung cancer cells. In the present study, an scAAV5 expressing a non‑cleavable human CD40L mutant (scAAV5‑CD40L‑M) was generated and its direct antitumor effects in lung cancer were evaluated. Transduction with scAAV5‑CD40L‑M resulted in effective expression of CD40L on the cell surface with low levels of cleaved sCD40L, which significantly reduced the percentage of viable cells and promoted caspase‑3‑dependent apoptosis of CD40‑positive lung carcinoma A549 cells, compared with scAAV5‑CD40L transduction (P<0.05). Furthermore, treatment with scAAV5‑CD40L‑M exerted a significant antitumor effect against CD40‑positive A549 xenografts by inducing apoptosis (P<0.05) with few side effects. Gene therapy using an scAAV5 vector expressing non‑cleavable human CD40L mutant may therefore have direct antitumor effects against CD40‑positive lung cancers. These tumoricidal effects of scAAV5‑CD40L‑M treatment make it a promising therapeutic technique for the treatment of lung cancer.
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January-2015
Volume 11 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Xu W, Xu Y, Wei Y, Tan Y, Zhao H, Zhao W and Wu J: Self‑complementary adeno‑associated virus 5‑mediated gene transduction of a novel CD40L mutant confers direct antitumor effects in lung carcinoma. Mol Med Rep 11: 482-488, 2015
APA
Xu, W., Xu, Y., Wei, Y., Tan, Y., Zhao, H., Zhao, W., & Wu, J. (2015). Self‑complementary adeno‑associated virus 5‑mediated gene transduction of a novel CD40L mutant confers direct antitumor effects in lung carcinoma. Molecular Medicine Reports, 11, 482-488. https://doi.org/10.3892/mmr.2014.2765
MLA
Xu, W., Xu, Y., Wei, Y., Tan, Y., Zhao, H., Zhao, W., Wu, J."Self‑complementary adeno‑associated virus 5‑mediated gene transduction of a novel CD40L mutant confers direct antitumor effects in lung carcinoma". Molecular Medicine Reports 11.1 (2015): 482-488.
Chicago
Xu, W., Xu, Y., Wei, Y., Tan, Y., Zhao, H., Zhao, W., Wu, J."Self‑complementary adeno‑associated virus 5‑mediated gene transduction of a novel CD40L mutant confers direct antitumor effects in lung carcinoma". Molecular Medicine Reports 11, no. 1 (2015): 482-488. https://doi.org/10.3892/mmr.2014.2765