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

Authors
 Pyung-Hwan Kim  ;  Joo-Hyuk Sohn  ;  Joung-Woo Choi  ;  Yukyung Jung  ;  Sung Wan Kim  ;  Seungjoo Haam  ;  Chae-Ok Yun 
Citation
 BIOMATERIALS, Vol.32(9) : 2314-2326, 2011 
Journal Title
BIOMATERIALS
ISSN
 0142-9612 
Issue Date
2011
MeSH
Adenoviridae/drug effects ; Adenoviridae/metabolism* ; Animals ; Antibodies, Monoclonal/adverse effects* ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/pharmacology* ; Antibodies, Monoclonal/toxicity ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/pharmacology ; Cell Death/drug effects ; Cell Line, Tumor ; Drug Delivery Systems/methods* ; Humans ; Immunity, Humoral/drug effects ; Immunity, Innate/drug effects ; Injections, Intravenous ; Liver/drug effects ; Liver/pathology ; Mice ; Oncolytic Viruses/drug effects ; Oncolytic Viruses/metabolism ; Polyethylene Glycols/chemistry* ; Receptor, ErbB-2/metabolism ; Tissue Distribution/drug effects ; Transduction, Genetic ; Trastuzumab ; Xenograft Model Antitumor Assays
Keywords
Cancer gene therapy ; Adenovirus ; Ad conjugated bioreducible polymer ; Hybrid vector ; Active targeting
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0142961210013384
DOI
10.1016/j.biomaterials.2010.10.031
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Pyung Hwan(김평환)
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
Choi, Joung Woo(최정우)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94349
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