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2007: Jung Yukyung; Park Hyo-Jin; Kim Pyung-Hwan; Lee Jaewon; Hyung Woochan; Yang Jaemoon; Ko Hyunju; Sohn Joo-Hyuk; Kim Joo-Hang; Huh Yong-Min; Yun Chae-Ok; Haam Seungjoo
Retargeting of adenoviral gene delivery via Herceptin-PEG-adenovirus conjugates to breast cancer cells.
Journal of controlled release : official journal of the Controlled Release Society 2007;123(2):164-71.
Targeted adenoviral gene delivery using human epidermal growth factor receptor 2 (HER2/neu) is one of the promising strategies for enhancing the transduction efficacy of PEGylated adenovirus (PEG-ADV). The viral capsid of adenovirus carrying the green fluorescent protein (GFP) was conjugated with bifunctional polyethylene glycol (PEG). The surface of PEG-ADV was then further conjugated with anti-HER2/neu monoclonal antibody (MAb), Herceptin (Trastuzumab; HER) to grant HER2/neu over-expressed breast cancer cells specific targeting. The PEG-ADV and Herceptin immobilized PEG-ADV (HER-PEG-ADV) extents of retargeting were evaluated, as compared to those of naked ADV. In summary, HER-PEG-ADV exhibited more enhanced level of GFP expression than PEG-ADV did for MDA-MB-435 and MDA-MB-468 cells (a HER2/neu positive cell line), but not for a HER2/neu deficient U251N cells. PEGylated ADV significantly reduced innate immune response likewise, as judged from the amount of interleukin 6 released from macrophage cells. Consequently, this study suggests that HER-PEG-ADV conjugates enable ADV to become more potential therapeutic tools through overcoming the limitation of ADV against immune system and non-specificity.

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