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

Pyung Hwan Kim, Joo Hyuk Sohn, Joung Woo Choi, Yukyung Jung, Sung Wan Kim, Seungjoo Haam, Chae Ok Yun

Research output: Contribution to journalArticle

58 Citations (Scopus)

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 1010-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.

Original languageEnglish
Pages (from-to)2314-2326
Number of pages13
JournalBiomaterials
Volume32
Issue number9
DOIs
Publication statusPublished - 2011 Mar 1

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Adenoviridae
Polyethylene glycols
Safety
Cells
Tumors
Plasmas
Gene therapy
Neutralizing Antibodies
Viruses
Antibodies
Liver
Trastuzumab
Interleukin-6
Neoplasms
Genetic Therapy
Virion
Therapeutics
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Kim, Pyung Hwan ; Sohn, Joo Hyuk ; Choi, Joung Woo ; Jung, Yukyung ; Kim, Sung Wan ; Haam, Seungjoo ; Yun, Chae Ok. / Active targeting and safety profile of PEG-modified adenovirus conjugated with herceptin. In: Biomaterials. 2011 ; Vol. 32, No. 9. pp. 2314-2326.
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Active targeting and safety profile of PEG-modified adenovirus conjugated with herceptin. / Kim, Pyung Hwan; Sohn, Joo Hyuk; Choi, Joung Woo; Jung, Yukyung; Kim, Sung Wan; Haam, Seungjoo; Yun, Chae Ok.

In: Biomaterials, Vol. 32, No. 9, 01.03.2011, p. 2314-2326.

Research output: Contribution to journalArticle

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