CD47-retargeted oncolytic adenovirus armed with melanoma differentiation-associated gene-7/interleukin-24 suppresses in vivo leukemia cell growth.
CD47-retargeted oncolytic adenovirus armed with melanoma differentiation-associated gene-7/interleukin-24 suppresses in vivo leukemia cell growth.
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携带黑色素瘤分化相关基因 7/白细胞介素 24 的 CD47 重靶向溶瘤腺病毒可抑制体内白血病细胞生长
DOI：
10.18632/oncotarget.6292
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发表时间：
2015-12-22
期刊：
影响因子：
--
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Li G;Wu H;Cui L;Gao Y;Chen L;Li X;Liang T;Yang X;Cheng J;Luo J
Our previous studies have suggested that harboring a soluble coxsackie-adenovirus receptor-ligand (sCAR-ligand) fusion protein expression cassette in the viral genome may provide a universal method to redirect oncolytic adenoviruses to various membrane receptors on cancer cells resisting to serotype 5 adenovirus infection. We report here a novel oncolytic adenovirus vector redirected to CD47+ leukemia cells though carrying a sCAR-4N1 expression cassette in the viral genome, forming Ad.4N1, in which 4N1 represents the C-terminal CD47-binding domain of thrombospondin-1. The infection and cytotoxicity of Ad.4N1 in leukemia cells were determined to be mediated by the 4N1-CD47 interaction. Ad.4N1 was further engineered to harbor a gene encoding melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), forming Ad.4N1-IL24, which replicated dramatically faster than Ad.4N1, and elicited significantly enhanced antileukemia effect in vitro and in a HL60/Luc xenograft mouse model. Our data suggest that Ad.4N1 could act as a novel oncolytic adenovirus vector for CD47+ leukemia targeting gene transfer, and Ad.4N1 harboring anticancer genes may provide novel antileukemia agents.
