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 language | English (US) |
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Pages (from-to) | 247-254 |
Number of pages | 8 |
Journal | Cancer Gene Therapy |
Volume | 19 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2012 |
Funding
This work was supported by the ‘Innovation Funds of Graduate Programs, Shaanxi Normal University’ (2009CXB009) and research Grants to H.X from National Natural Science Foundation of China (No.30872993 and No.31070137).
Keywords
- arresten
- conditionally replicating adenoviral vector
- interleukin-24
- malignant melanoma
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Cancer Research