Optimized PEGylated Adenovirus Vector Reduces the Anti-vector Humoral Immune Response against Adenovirus and Induces a Therapeutic Effect against Metastatic Lung Cancer
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概要
- 論文の詳細を見る
Application of adenovirus vectors (Adv) in metastatic cancer treatment is limited. We previously demonstrated that covalent conjugation of polyethleneglycol (PEG) to Adv enhances therapeutic effects and decreases toxic side-effects after systemic administration, but the level of immune response to PEGylated Adv (PEG-Ad) was not examined. Here, we examined the effect of PEGylation of Adv on the production of anti-Adv antibodies and antitumor response. We constructed a set of PEG-Ad using 5-kDa PEG, with modification rates of 30%, 45% and 90%. After systemic administration of Advs to rats, we examined the level of anti-Adv immunoglobulin (Ig)G and IgM in serum. The levels of anti-Adv IgG and anti-Adv IgM in rats treated with unmodified Adv were higher than those in control group. Rats treated with PEG-Ad that had a 90% modification rate showed lower level of anti-Adv IgG and anti-Adv IgM than those treated with unmodified Adv, whereas rats treated with PEG-Ad that had a 30% or 45% modification rate showed a similar level of anti-Adv IgG and IgM to those treated with unmodified Adv. Systemic administration of PEG-Ad that had a 90% modification rate, and expressed tumor necrosis factor-α, significantly reduced the number of metastatic colonies in the lung compared to unmodified Adv, with negligible side effects. These results suggest that systemic administration of PEG-Ad with an appropriate PEG modification rate has the potential to reduce the production of antibodies against Adv and increase the therapeutic response against metastatic cancer.
著者
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Yoshioka Yasuo
Department of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka Unive
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Eto Yusuke
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka Univ
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Ishida Tatsuhiro
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Inst
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Yao Xinglei
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka Univ
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Morishige Tomohiro
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka Univ
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Narimatsu Shogo
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka Univ
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Mizuguchi Hiroyuki
Department of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka
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Mukai Yohei
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka Univ
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Okada Naoki
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka Univ
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Kiwada Hiroshi
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Inst
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Nakagawa Shinsaku
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka Univ
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Eto Yusuke
Department Of Biotechnology And Therapeutics Graduate School Of Pharmaceutical Sciences Osaka Univer
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Eto Yusuke
大阪大学 薬研究
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Yoshioka Yasuo
Department Of Radiation Oncology Osaka University Graduate School Of Medicine
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Yoshioka Yasuo
大阪大学 医学系研究科放射線治療学
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Kiwada Hiroshi
Department Of Pharmacokinetics And Biopharmaceutics Faculty Of Pharmaceutical Sciences The Universit
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Yoshioka Yasuo
Dept. Of Radiation Oncology Osaka University Graduate School Of Medicine
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Nakagawa Shinsaku
Department Of Biopharmaceutics Graduate School Of Pharmaceutical Sciences Osaka University
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Okada Naoki
Department Of Bioppharmaceutics Kyoto Pharmaceutical University
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Yamashiro Y
Osaka Univ. Suita Jpn
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Ishida Tatsuhiro
Department Of Pharmacokinetics And Biopharmaceutics Institute Of Health Biosciences The University O
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Okada Naoki
Department Of Biopharmaceutics Kyoto Pharmaceutical University
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Nakagawa Shinsaku
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University
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Narimatsu Shogo
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University
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Okada Naoki
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University
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Morishige Tomohiro
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University
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Eto Yusuke
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University
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Yao Xinglei
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University
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Yoshioka Yasuo
Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University
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