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.
|Number of pages||13|
|Publication status||Published - 2011 Mar|
Bibliographical noteFunding Information:
This work was supported by grants from the Ministry of Knowledge Economy ( 10030051 , Dr. C-O Yun), the National Research Foundation of Korea (R15-2004-024-02001-0, 2010-0029220, 2009K001644, Dr. C-O Yun), and a faculty research grant (6-2007-0114, Dr. J-H Sohn) from Yonsei University College of Medicine . Pyung-Hwan Kim, Yukyung Jung, and Joung-Woo Choi are graduate students sponsored by NRF through National Core Research Center for Nanomedical Technology, Yonsei University, Seoul, South Korea .
All Science Journal Classification (ASJC) codes
- Ceramics and Composites
- Mechanics of Materials