CD47-retargeted oncolytic adenovirus armed with melanoma differentiation-associated gene-7/interleukin-24 suppresses in vivo leukemia cell growth
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Gongchu Li1, Hu Wu1, Lianzhen Cui1, Yajun Gao1, Lei Chen1, Xin Li1, Tianxiang Liang1, Xinyan Yang1, Jianhong Cheng1, Jingjing Luo1
1College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China
Gongchu Li, e-mail: [email protected]
Keywords: oncolytic adenovirus, CD47, thrombospondin-1, leukemia, interleukin-24
Received: May 07, 2015 Accepted: October 23, 2015 Published: November 02, 2015
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.
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