Development of Immunomodulatory Cytokine mutants

• Project/Area Number: 22790180
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: ABE Yasuhiro 独立行政法人医薬基盤研究所, 創薬基盤研究部バイオ創薬プロジェクト, 研究員 (20509898)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 免疫誘導療法 / ファージ表面提示法 / サイトカイン / インターフェロン

Research Abstract

Type I interferons(IFNs) are pleiotropic cytokines that elicit antiviral and antiproliferative responses. In this study, we attempted to create a mutant IFN with higher anti-viral activity. At first, we constructed a phage library displaying IFN mutants. The phage library was performed to several rounds of panning to concentrate mutatnt IFN with high affinity to IFN receptor. As the results, some candidates exhibited higher affinity and anti-viral activity compare to wild type IFN.

Research Products

• [Journal Article] Fine tuning of receptor-selectivity for tumor necrosis factor-a using a phage display system with one-step competitive panning (2011)
  • Author(s): Abe Y, Yoshikawa T, et al
  • Journal Title: Biomaterials Volume: 32(23) Issue: 23 Pages: 5498-5504
  • DOI: 10.1016/j.biomaterials.2011.04.018
  • Peer Reviewed
• [Journal Article] Development of a novel antibody proteomics system using a phage antibody library for efficient screening of tumor-related biomarker proteins (2011)
  • Author(s): Imai S, Nagano K, Yoshida Y, Okamura T, Yamashita T, Abe Y, Yoshikawa T, Yoshioka Y, Kamada H, Mukai Y, Nakagawa S, Tsutsumi Y, Tsunoda S
  • Journal Title: Biomaterials Volume: 32 Issue: 1 Pages: 162-169
  • DOI: 10.1016/j.biomaterials.2010.09.030
  • Peer Reviewed
• [Journal Article] Development of a novel antibody proteomics system using a phage antibody library for efficient screening of tumor-related biomarker proteins. (2011)
  • Author(s): Imai S., Nagano K., Yoshida Y., Okamura T., Yamashita T., Abe Y., Yoshikawa T., Yoshioka Y., Kamada H., Mukai Y., Nakagawa S., Tsutsumi Y., Tsunoda S.
  • Journal Title: Biomaterials Volume: 32(1) Pages: 162-169
  • Peer Reviewed
• [Journal Article] The IL-1 family cytokines as mucosal vaccine adjuvant for the induction of protective immunity against influenza virus (2010)
  • Author(s): Kayamuro H., Yoshioka Y., Abe Y., Arita S., Katayama K., Nomura T., Yoshikawa T., Kubota-Koketsu R., Ikuta K., Okamoto S., Mori Y., Kunisawa J., Kiyono H., Itoh N., Nagano K., Kamada H., Tsutsumi Y., Tsunoda S.
  • Journal Title: J Virol. Volume: 84(24) Issue: 24 Pages: 12703-12
  • DOI: 10.1128/jvi.01182-10
  • Peer Reviewed
• [Journal Article] The IL-1 family cytokines as mucosal vaccine adjuvant for the induction of protective immunity against influenza virus. (2010)
  • Author(s): Kayamuro H., Yoshioka Y., Abe Y., Arita S., Katayama K., Nomura T., Yoshikawa T., Kubota-Koketsu R., Ikuta K., Okamoto S., Mori Y., Kunisawa J., Kiyono H., Itoh N., Nagano K., Kamada H., Tsutsumi Y., Tsunoda S.
  • Journal Title: J.Virol. Volume: 84(24) Pages: 12703-12
  • Peer Reviewed
• [Presentation] Biological and structural characterization of human TNFR2-selective TNF mutants (2011)
  • Author(s): Abe Y., Inoue M., Furuya T., Mukai Y., Nakamura T., Yamagata Y., Nabeshi H., Yoshikawa T., Yoshioka Y., Nagano K., Kamada H., Tsutsumi Y., Tsunoda S.
  • Organizer: 9th Joint Meeting of ICS-ISICR(Cytokines2011)
  • Place of Presentation: Florence(Italy)
• [Presentation] Selective inhibition of TNFR1 by mutant TNF with antagonistic activity is effective in the treatment of experimental autoimmune encephalomyelitis (2011)
  • Author(s): Abe Y., Nomura T., Inoue M., Furuya T., Arita S., Nabeshi H., Yoshikawa T., Yoshioka Y., Nagano K., Kamada H., Tsutsumi Y., Tsunoda S.
  • Organizer: 13th International TNF Conference
  • Place of Presentation: Awaji(Japan)
• [Presentation] Biological and structural characterization of human TNFR2-selective TNF mutants (2011)
  • Author(s): Abe Y, Inoue M, Furuya T, Mukai Y, Nakamura T, Yamagata Y, Nabeshi H, Yoshikawa T, Yoshioka Y, Nagano K, Kamada H, Tsutsumi Y, Tsunoda S
  • Organizer: 9th Joint Meeting of ICS-ISICR (Cytokines2011)
  • Place of Presentation: Florence (Italy)
• [Presentation] Selective inhibition of TNFR1 by mutant TNF with antagonistic activity is effective in the treatment of experimental autoimmune encephalomyelitis (2011)
  • Author(s): Abe Y, Nomura T, Inoue M, Furuya T, Arita S, Nabeshi H, Yoshikawa T, Yoshioka Y, Nagano K, Kamada H, Tsutsumi Y, Tsunoda S
  • Organizer: 13th International TNF Conference
  • Place of Presentation: Awaji (Japan)
• [Presentation] レセプター特異性に優れた機能性人工質蛋白質創出システムの開発 (2010)
  • Author(s): 阿部康弘,井上雅己,野村鉄也,有田修平,古屋剛,長野一也,鎌田春彦,角田慎一,堤康央
  • Organizer: 第26回日本DDS学会学術集会
  • Place of Presentation: 大阪