title: CD47-retargeted oncolytic adenovirus armed with melanoma differentiation-associated gene-7/interleukin-24 suppresses in vivo leukemia cell growth.
abstract: 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.
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Gongchu
authors.initials: G
authors.lastname: Li
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Wu
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Lianzhen
authors.initials: L
authors.lastname: Cui
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Liang
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Cheng
authors.affiliation: College of life sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Luo
mesh_terms: D000256:Adenoviridae; D000818:Animals; D015153:Blotting, Western; D051928:CD47 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D007938:Leukemia; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D050130:Oncolytic Virotherapy / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
chemical_list: D051928:CD47 Antigen; D007378:Interleukins; D011993:Recombinant Fusion Proteins; D000099180:Interleukin-24
keywords: CD47; interleukin-24; leukemia; oncolytic adenovirus; thrombospondin-1