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Active targeting and safety profile of PEG-modified adenovirus conjugated with herceptin

Title
Active targeting and safety profile of PEG-modified adenovirus conjugated with herceptin
Author
윤채옥
Keywords
Cancer gene therapy; Adenovirus; Ad conjugated bioreducible polymer; Hybrid vector; Active targeting
Issue Date
2011-03
Publisher
ELSEVIER SCI LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
Citation
Biomaterials,Vol.32 No.9 [2011],2314-2326
Abstract
PEGylation of adenovirus (Ad) increases plasma retention and reduces immunogenicity, but decreases the accessibility of virus particles to target cells. We tested whether PEGylated Ad conjugated to Herceptin (Ad-PEG-HER) can be used to treat Her2/neu-positive cells in vitro and in vivo to demonstrate the therapeutic feasibility of this Ad formulation. Ad-PEG-HER transduced Her2/neu-overexpressing cancer cells through a specific interaction between Herceptin and Her2/neu. Ad-PEG-HER treatment resulted in higher plasma retention and lower neutralizing antibody and IL-6 production than naked Ad. This formulation was extended to generate a Her2/neu-targeted, PEGylated oncolytic Ad (DWP418-PEG-HER). DWP418-PEG-HER specifically killed Her2/neu-positive cells and performed better than non-targeted and naked Ad in vivo. DWP418-PEG-HER showed a 10(10)-fold increase in the liver to tumor biodistribution compared with naked Ad. Immunohistochemical staining confirmed accumulation of Ad E1A in tumors. These data suggest that targeted gene therapy with the PEGylated Ad conjugated with Herceptin might shed a light on its therapeutic application for metastatic cancer in the future. (C) 2010 Elsevier Ltd. All rights reserved.
URI
http://www.sciencedirect.com/science/article/pii/S0142961210013384?via%3Dihub
ISSN
0142-9612
DOI
10.1016/j.biomaterials.2010.10.031
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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