Development of novel claudin-4 binder and its application in oral vaccine

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790155
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Osaka University
• Principal Investigator: WATARI Akihiro 大阪大学, 薬学研究科(研究院), 助教 (80452465)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: ワクチン / claudin / DDS

Research Abstract

We prepared C-CPE mutant, which had higher affinity for claudin-4 than C-CPE, and made a fusion protein with the C-CPE mutant and ovalbumin (OVA) as a model antigen. Immunization with the C-CPE mutant-fused OVA led to increased anti-tumor activity relative to that of mice immunized with the C-CPE-fused OVA. The liposomes modified with the C-CPE mutant bind to CL-4-expressing cells and targeted to Peyer's patch cells in mouse intestine. These findings suggest that the modified liposome shows promise as a claudin-targeted oral vaccine.

Research Products

• [Journal Article] Tissue distribution and safety evaluation of a claudin-targeting molecule, the C-terminal fragment of Clostridium perfringens enterotoxin (2014)
  • Author(s): Li X., Saeki R., Watari A., Yagi K., Kondoh M
  • Journal Title: Eur J Pharm Sci Volume: 52 Pages: 132-7
• [Journal Article] A baculoviral display system to assay viral entry (2013)
  • Author(s): I ida M., Yoshida T., Watari A., Yagi K., Hamakubo T., Kondoh M
  • Journal Title: Biol Pharm Bull Volume: 36(11) Pages: 1867-9
• [Journal Article] Acute and chronic nephrotoxicity of platinum nanoparticles in mice (2013)
  • Author(s): Yamagishi Y., Watari A., Hayata Y., Li X., Kondoh M., Yoshioka Y., Tsutsumi Y., Yagi K
  • Journal Title: Nanoscale Res Lett Volume: 8(1) Pages: 395
• [Journal Article] Hepatotoxicity of sub-nanosized platinum particles in mice (2013)
  • Author(s): Yamagishi Y., Watari A., Hayata Y., Li X., Kondoh M., Tsutsumi Y., Yagi K
  • Journal Title: Pharmazie Volume: 69(3) Pages: 179-82
• [Journal Article] Involvement of NANOG upregulation in malignant progression of human cells (2013)
  • Author(s): Li Y., Higashiyama S., Shimakage M., Kawahara K., Yutsudo M., Watari A
  • Journal Title: DNA Cell Biol Volume: 32(3) Pages: 104-10
• [Journal Article] Nature of cancer explored from the perspective of the functional evolution of proto-oncogenes (2012)
  • Author(s): Watari A.
  • Journal Title: Yakugaku Zasshi Volume: 132(10) Pages: 1165-70
• [Journal Article] A simple reporter assay for screening claudin-4 modulators (2012)
  • Author(s): Watari A., Yagi K., Kondoh M
  • Journal Title: Biochem Biophys Res Commun Volume: 426(4) Pages: 454-60
• [Journal Article] Pathological changes in tight junctions and potential applications into therapies (2012)
  • Author(s): Takahashi A., Kondoh M., Suzuki H., Watari A. and Yagi K.
  • Journal Title: Drug Discov. Today Volume: 17(13-14) Pages: 727-32
• [Journal Article] A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF (2012)
  • Author(s): Watari A., Li Y., Higashiyama S., Yutsudo M
  • Journal Title: Exp Cell Res Volume: 18(3) Pages: 187-95
• [Presentation] Identification of chemical compounds that modulate claudin-4 expression by cell-based screening (2013)
  • Author(s): Watari A., Hasegawa M., Yagi K., Kondoh M
  • Organizer: The American society for Cell Biology
  • Place of Presentation: New Orleans, U.S.A
  • Year and Date: 20131214-18
• [Presentation] Tissue-distribution and safety evaluation of a claudin-3/4 binder in mice (2013)
  • Author(s): Li X., Watari A., Yagi K., Kondoh M
  • Organizer: The American society for Cell Biology
  • Place of Presentation: New Orleans, U.S.A.
  • Year and Date: 20131214-18
• [Presentation] タイトジャンクションを標的とした創薬基盤研究 (2013)
  • Author(s): 8.渡利彰浩、近藤昌夫、八木清仁
  • Organizer: 第19回ハインガットクラブジャパンシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20131200
  • Invited
• [Presentation] Creation of a broadly specific claudin binder and its absorption-enhancing actibity (2013)
  • Author(s): Doyama R., Matsuhisa K., Takahashi A., Matsuhisa K., Watari A., Hamakubo T., Yagi K., Kondoh M
  • Organizer: 2013 AAPS Annual Meeting and Exposition
  • Place of Presentation: San Antonio, U.S.A.
  • Year and Date: 20131110-14
• [Presentation] An improved claudin-targeting mucosal vaccine using a double alanine-substituted Mutant of the C-terminal fragment of Clostridium perfringens enterotoxin (2013)
  • Author(s): Suzuki H., Kunisawa J., Watari A., Yamashita M., Yagi K., Kondoh M
  • Organizer: 40th Annual Meeting & Exposition of the Controlled Release Society 2013
  • Place of Presentation: Honolulu, HI, U.S.A.
  • Year and Date: 20130721-24
• [Presentation] Claudinを標的とした粘膜ワクチン技術の開発 (2013)
  • Author(s): 土山遼、鈴木英彦、角谷英樹、渡利彰浩、近藤昌夫、八木清仁
  • Organizer: 第32回分子病理研究会
  • Place of Presentation: 奈良県,吉野町
  • Year and Date: 20130700
• [Presentation] Claudin-3 and -4 binderの体内動態解析および安全性評価 (2013)
  • Author(s): 李相儒、近藤昌夫、渡利彰浩、八木清仁
  • Organizer: 第32回分子病理研究会
  • Place of Presentation: 奈良県,吉野町
  • Year and Date: 20130700
• [Presentation] Tissue-distribution of claudin-3/-4 binder, the C-terminal fragment of Clostridium perfringens enterotoxin, in mice (2013)
  • Author(s): Li X., Kondoh M., Watari A. and Yagi K
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 20130420-24
• [Presentation] Establishment of a cell-based screening system for chemical modulators of claudin expression (2012)
  • Author(s): Watari A., Hasegawa M., Kondoh M. and Yagi K., ., , Dec 1-4
  • Organizer: Molecular Structure and Function of the Apical Junctional Complex in Epithelia and Endothelia
  • Place of Presentation: Merida, MEXICO
  • Year and Date: 20121201-04
• [Presentation] Biochemical analysis of a claudin ligand that exhibits a broad binding specificity (2012)
  • Author(s): Doyama R., Suzuki H., Matsushita K., Li X, Takahashi A., Matsuhisa K., Tsujino H., Watari A., Kondoh M., Aoyama H., Uno T. and Yagi K
  • Organizer: Molecular Structure and Function of the Apical Junctional Complex in Epithelia and Endothelia
  • Place of Presentation: Merida, MEXICO
  • Year and Date: 20121201-04
• [Presentation] Evaluation of HCV infection and replication using human iPS cell-derived hepatocytes (2012)
  • Author(s): Yagi K., Yoshida T., Yamane S., Takayama K., Watari A., Kondoh M., Sakurai F., Sakamoto N., Mtsuura Y., Mizuguchi H
  • Organizer: HCV2012 19th International Symposium on Hepatittis C virus and Relate viruses
  • Place of Presentation: Venice, ITALY
  • Year and Date: 20121005-09
• [Presentation] 原がん遺伝子の機能進化から探る新たながん化メカニズムの解析 (2012)
  • Author(s): 渡利彰浩、岡田雅人、八木清仁
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 西宮,兵庫県
  • Year and Date: 20121000
• [Presentation] Clostridium perfringens enterotoxin断片を利用したclaudin指向性吸収促進技術の安全性評価 (2012)
  • Author(s): 土山亮、長瀬翔太郎、鈴木英彦、李相儒、山根誠司、渡利彰浩、近藤昌夫、八木清仁
  • Organizer: 第59回トキシンシンポジウム
  • Place of Presentation: 北海道,帯広市
  • Year and Date: 20120800
• [Presentation] 高親和性claudin-4 binderの創製と粘膜ワクチンへの応用 (2012)
  • Author(s): 鈴木英彦、山根誠司、角谷英樹、高橋梓、内田博司、渡利彰浩、近藤昌夫、八木清仁
  • Organizer: 第28回DDS学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20120700
• [Presentation] Preparation of a broad-specific claudin binder by using Clotridium perfringens enterotoxin (2012)
  • Author(s): Suzuki H., Takahashi A., Matsushita K., Li X., Tsujino H., Watari A., Kondoh M., Aoyama H., Uno T. and Yagi K
  • Organizer: Experimental Biology 2012
  • Place of Presentation: SanDiego, U.S.A.
  • Year and Date: 20120421-25
• [Remarks]
  • URL: https://sites.google.com/site/yakugakuseitaikinoubunshi/