A novel conditionally replicating adenoviral vector with dual expression of IL-24 and arresten inserted in E1 and the region between E4 and fiber for improved melanoma therapy

L. Chai, S. Liu, Qinwen Mao, D. Wang, X. Li, X. Zheng, H. Xia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Although the combination of gene therapy and virotherapy for cancer therapy has obtained some encouraging results in vitro and in vivo over the past few years, some improvements of the vectors are still urgently needed to enhance their therapeutic effects for cancers. In order to maximize the anti-cancer activities of conditionally replicating adenoviral vectors (CRAd) vector, we for the first time generated a novel CRAd vector by inserting an expression cassette between E4 and the fiber using homologous recombination and tested this vector in melanoma cancer therapy. By using this novel vector we expressed two therapeutic transgenes, IL-24 and arresten, inserted in E1 and the region between E4 and the fiber, respectively, to test the melanoma inhibitory activities of this oncolytic virus in vitro and in vivo. The two therapeutic transgenes were successfully expressed by the novel CRAd, which was confirmed by western blotting. We then showed that this novel CRAd vector significantly suppressed the tumor growth of melanoma in vitro and in vivo compared with the control by inducing apoptosis and inhibiting angiogenesis. The novel CRAd vector generated in this study holds promise for developing more effective therapeutics for not only melanoma but also other common cancers.

Original languageEnglish (US)
Pages (from-to)247-254
Number of pages8
JournalCancer Gene Therapy
Volume19
Issue number4
DOIs
StatePublished - Apr 1 2012

Keywords

  • arresten
  • conditionally replicating adenoviral vector
  • interleukin-24
  • malignant melanoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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