Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics*
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Adenoviridae / immunology
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Animals
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Antibodies, Monoclonal / chemistry
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Antibodies, Monoclonal / metabolism
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / therapy*
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Cell Line, Tumor
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Chromatography, Liquid
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Feasibility Studies
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Female
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Flow Cytometry
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Gene Expression Regulation, Neoplastic
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Genes, Reporter
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Genetic Therapy / methods*
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Genetic Vectors* / immunology
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Green Fluorescent Proteins / genetics
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Humans
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Interleukin-6 / metabolism
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Light
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Microscopy, Electron, Transmission
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Polyethylene Glycols / chemistry*
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / metabolism
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Scattering, Radiation
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Transduction, Genetic*
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Trastuzumab
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Interleukin-6
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Green Fluorescent Proteins
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Polyethylene Glycols
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Receptor, ErbB-2
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Trastuzumab