Targeting eradication of chronic myeloid leukemia using chimeric oncolytic adenovirus to drive IL-24 expression |
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Authors: | Xubin Wei Li liu Gang Wang Wei Li Ke Xu Xupang Hu Cheng Qian Jimin Shao |
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Affiliation: | 1.Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Zhejiang 310058, Hangzhou;2.School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, P. R. China |
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Abstract: | Chronic myeloid leukemia (CML) is a clonal disorder in which cells of the myeloid lineage undergo massive clonal expansion as well as resistance to conventional chemotherapy. Gene therapy hold a great promise for treatment of malignancies based on the transfer of genetic material to the tissues. In this study, we explore whether chimeric oncolytic adenovirus-mediated transfer of human interleukin-24 (IL-24) gene induce the enhanced antitumor potency. Our results showed that chimeric oncolytic adenovirus carrying hIL-24 (AdCN205-11-IL-24) could produce high levels of hIL-24 in CML cancer cells, as compared with constructed double-regulated oncolytic adenovirus expressing hIL-24 (AdCN205-IL-24). AdCN205-11-IL-24 could specifically induce cytotoxocity to CML cancer cells, but little or no effect on normal cell lines. AdCN205-11-IL-24 exhibited remarkable anti-tumor activities and induce higher antitumor activity to CML cancer cells by inducing apoptosis in vitro. Our study may provides a potent and safe tool for CML gene therapy. |
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Keywords: | Chimeric oncolytic adenovirus chronic myeloid leukemia fiber IL-24 gene gene-therapy |
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