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Targeting eradication of chronic myeloid leukemia using chimeric oncolytic adenovirus to drive IL-24 expression
Authors:Xubin Wei  Li liu  Gang Wang  Wei Li  Ke Xu  Xupang Hu  Cheng Qian  Jimin Shao
Institution: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
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.
Keywords:Chimeric oncolytic adenovirus  chronic myeloid leukemia  fiber  IL-24 gene  gene-therapy
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