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A vesicular stomatitis virus glycoprotein epitope-incorporated oncolytic adenovirus overcomes CAR-dependency and shows markedly enhanced cancer cell killing and suppression of tumor growth

Title
A vesicular stomatitis virus glycoprotein epitope-incorporated oncolytic adenovirus overcomes CAR-dependency and shows markedly enhanced cancer cell killing and suppression of tumor growth
Author
윤아름
Keywords
oncolytic adenovirus; VSVG; fiber; CAR dependency; therapeutic efficacy
Issue Date
2015-10
Publisher
IMPACT JOURNALS LLC
Citation
ONCOTARGET v.6, no.33, Page. 34875-34891
Abstract
Utility of traditional oncolytic adenovirus (Ad) has been limited due to low expression of coxsackie and adenovirus receptor (CAR) in cancer cells which results in poor infectivity of Ads. Here with an aim of improving the efficiency of Ad's entry to the cell, we generated a novel tropism-expanded oncolytic Ad which contains the epitope of vesicular stomatitis virus glycoprotein (VSVG) at the HI-loop of Ad fiber. We generated 9 variants of oncolytic Ads with varying linkers and partial deletion to the fiber. Only one VSVG epitope-incorporated variant, RdB-1L-VSVG, which contains 1 linker and no deletion to fiber, was produced efficiently. Production of 3-dimensionaly stable fiber in RdB-1L-VSVG was confirmed by immunoblot analysis. RdB-1L-VSVG shows a remarkable improvement in cytotoxicity and total viral yield in cancer cells. RdB-1L-VSVG demonstrates enhanced cytotoxicity in cancer cells with subdued CAR-expression as it can be internalized by an alternate pathway. Competition assays with a CAR-specific antibody (Ab) or VSVG receptor, phosphatidyl serine (PS), reveals that cell internalization of RdB-1L-VSVG is mediated by both CAR and PS. Furthermore, treatment with RdB-1L-VSVG significantly enhanced anti-tumor effect in vivo. These studies demonstrate that the strategy to expand oncolytic Ad tropism may significantly improve therapeutic profile for cancer treatment.
URI
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=5332http://hdl.handle.net/20.500.11754/28062
ISSN
1949-2553
DOI
10.18632/oncotarget.5332
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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