Development of synthetic adjuvants by biological drug design

• Project/Area Number: 21790400
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
• Principal Investigator: AKAZAWA Takashi Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses, 研究所, 研究員 (80359299)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 腫瘍 / 腫瘍免疫 / アジュバント / BCG-CWS / 創薬設計 / 自然免疫 / Toll-like receptor / がん免疫療法 / 樹状細胞

Research Abstract

It is essential to develop effective immunoadjuvants for tumor immunotherapy. We created new adjuvants based on the structure of mycoplasmal lipopeptide, which is a toll-like receptor (TLR) 2 ligand. Adjuvant engineering, substituting a functional motif for bacterial origin sequence of lipopeptide, is a novel drug design strategy. Here, we report the characterization of a new TLR2 ligand with complexation capability.

Research Products

• [Journal Article] Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. (2011)
  • Author(s): Sawahata R, Shime H, Yamazaki S, Inoue N, Akazawa T, Fujimoto Y, Fukase K, Matsumoto M, Seya T.
  • Journal Title: Microbes Infect. 13(4) Pages: 350-8
  • NAID: 120002912001
  • Peer Reviewed
• [Journal Article] IL-23-dependent and -independent enhancement pathways of IL-17A production by lactic acid. (2011)
  • Author(s): Yabu M, Shime H, Hara H, Saito T, Matsumoto M, Seya T, Akazawa T, Inoue N.
  • Journal Title: Int Immunol. 23(1) Pages: 29-41
  • Peer Reviewed
• [Journal Article] Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. (2011)
  • Author(s): Sawahata R, Shime H, Yamazaki S, Inoue N, Akazawa T, Fujimoto Y, Fukase K, Matsumoto M, Seya T.
  • Journal Title: Microbes and Infection Volume: 13(4) Pages: 128-132
  • NAID: 120002912001
  • Peer Reviewed
• [Journal Article] IL-23-dependent and -independent enhancement pathways of IL-17A production by lactic acid. (2011)
  • Author(s): Yabu M, Shime H, Hara H, Saito T, Matsumoto M, Seya T, Akazawa T, Inoue N.
  • Journal Title: International Immunology. Volume: 23(1) Pages: 29-41
  • Peer Reviewed
• [Journal Article] IFN-gamma markedly cooperates wiintratumoral dendritic cell vaccine in dog tumor models. (2010)
  • Author(s): Mito K, Sugiura K, Ueda K, Hori T, Akazawa T, Yamate J, Nakagawa H, Hatoya S, Inaba M, Inoue N, Ikehara S, Inaba T.
  • Journal Title: Cancer Res. 70(18) Pages: 7093-101
  • Peer Reviewed
• [Journal Article] Effect of IL-12 on canine dendritic cell maturation following differentiation induced by granulocyte-macrophage CSF and IL-4. (2010)
  • Author(s): Sugiura K, Wijewardana V, Fujimoto M, Akazawa T, Yahata M, Mito K, Hatoya S,Inoue N, Inaba T.
  • Journal Title: Vet Immunol Immunopathol. 137(3-4) Pages: 322-6
  • Peer Reviewed
• [Journal Article] Adjuvant engineering for cancer immunotherapy : Development of a synthetic TLR2 ligand with increased cell adhesion. (2010)
  • Author(s): Akazawa T, Inoue N, Shime H, Kodama K, Matsumoto M, Seya T.
  • Journal Title: Cancer Sci. 101(7) Pages: 1596-603
  • NAID: 10026594411
  • Peer Reviewed
• [Journal Article] Two-stecolocalization of MORC3 with PML nuclear bodies. (2010)
  • Author(s): Mimura Y, Takahashi K, Kawata K, Akazawa T, Inoue N.
  • Journal Title: J Cell Sci. 123(Pt12) Pages: 2014-24
  • Peer Reviewed
• [Journal Article] IFN-gamma markedly cooperates with intratumoral dendritic cell vaccine in dog tumor models. (2010)
  • Author(s): Mito K, Sugiura K, Ueda K, Hori T, Akazawa T, Yamate J, Nakagawa H, Hatoya S, Inaba M, Inoue N, Ikehara S, Inaba T.
  • Journal Title: Cancer Research. Volume: 70(18) Pages: 7093-7101
  • Peer Reviewed
• [Journal Article] Effect of IL-12 on canine dendritic cell maturation following differentiation induced by granulocyte-macrophage CSF and IL-4. (2010)
  • Author(s): Sugiura K, Wijewardana V, Fujimoto M, Akazawa T, Yahata M, Mito K, Hatoya S, Inoue N, Inaba T.
  • Journal Title: Veterinary Immunology and Immunopathology Volume: 137(3-4) Pages: 322-326
  • Peer Reviewed
• [Journal Article] Adjuvant engineering for cancer immunotherapy : development of a synthetic TLR2 ligand with increased cell adhesion. (2010)
  • Author(s): Akazawa T, Inoue N, Shime H, Kodama K, Matsumoto M, Seya T.
  • Journal Title: Cancer Science Volume: 101(7) Pages: 1596-1603
  • NAID: 10026594411
  • Peer Reviewed
• [Journal Article] Two-step colocalization mechanism of MORC3 with PML-nuclear body. (2010)
  • Author(s): Mimura Y, Takahashi K, Kawata K, Akaawa T, Inoue N.
  • Journal Title: Journal of Cell Science Volume: 123(pt12) Pages: 2014-2024
  • Peer Reviewed
• [Journal Article] djuvant engineering for cancer immunotherapy : development of a synthetic TLR2 ligand with increased cell adhesion. (2010)
  • Author(s): Akazawa T, Inoue N, Shime H, Kodama K, Matsumoto M, Seya T.
  • Journal Title: Cancer Science (In press)
  • Peer Reviewed
• [Journal Article] Two-step colocalization mechanism of MORC3 with PML-nuclear body. (2010)
  • Author(s): Mimura Y, Takahashi K, Kawata K, Akaawa T, Inoue N.
  • Journal Title: Journal of Cell Science (In press)
  • Peer Reviewed
• [Journal Article] Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice (2009)
  • Author(s): Akao Y, Ebihara T, Masuda H, Saeki Y, Akazawa T, Hazeki K, Hazeki O, Matsumoto M, Seya T.
  • Journal Title: Cancer Sci. 100(8) Pages: 1494-501
  • NAID: 10027193541
  • Peer Reviewed
• [Journal Article] Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice. (2009)
  • Author(s): Akao Y, Ebihara T, Masuda H, Saeki Y, Akazawa T, Hazeki K, Hazeki O, Matsumoto M, Seya T.
  • Journal Title: Cancer Science 100(8) Pages: 1494-1501
  • NAID: 10027193541
  • Peer Reviewed
• [Presentation] Adjuvant engineering for cancer immunotherapy : development of a synthetic TLR2 ligand with alternative functions. (2010)
  • Author(s): Akazawa T, Inoue N.
  • Organizer: 5^<th> International Peptide Symposium
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-12-05
• [Presentation] Adjuvant engineering for cancer immunotherapy : development of a synthetic TLR2 ligand with alternative functions. (2010)
  • Author(s): Akazawa T, Kodama K, Matsumoto M, Seya T, Inoue N.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Adjuvant engineering for cancer immunotherapy: development of a synthetic TLR2 ligand with alternative functions. (2010)
  • Author(s): Akazawa T, Inoue N.
  • Organizer: 第5回国際ペプチドシンポジウム(ポスター)
  • Place of Presentation: 京都
• [Presentation] Adjuvant engineering for cancer immunotherapy: development of a synthetic TLR2 ligand with additional function. (2010)
  • Author(s): Akazawa T, Inoue N, Shime H, Kodama K, Matsumoto M, Seya T.
  • Organizer: 第14回国際免疫学会(ポスター)
  • Place of Presentation: 神戸
• [Presentation] Adjuvant engineering for cancer immunotherapy: development of a synthetic TLR2 ligand with alternative functions. (2010)
  • Author(s): Akazawa T, Inoue N, Kodama K, Matsumoto M, Seya T.
  • Organizer: 第69回日本癌学会学術総会(ポスター)
  • Place of Presentation: 大阪
• [Presentation] A synthetic TLR2 ligand containing the RGD motif works as an effective adjuvant. (2009)
  • Author(s): Akazawa T, Inoue N, Shime H, Kodama K, Matsumoto M, Seya T.
  • Organizer: 第68回日本癌学会学術総会(ポスター)
  • Place of Presentation: 横浜
• [Presentation] インテグリン結合モチーフを含む人工設計リポペプチドはトル様受容体2のリガンドとして機能し、効果的なアジュバント活性を持つ (2009)
  • Author(s): 赤澤隆
  • Organizer: 第13回日本がん免疫学会(一般口演)
  • Place of Presentation: 北九州
• [Presentation] A synthetic TLR2 ligand containing the RGD motif works as an effective adjuvant. (2009)
  • Author(s): Akazawa T, Inoue N, Shime H, Kodama K, Matsumoto M, Seya T.
  • Organizer: 第68回日本癌学会
  • Place of Presentation: パシフィコ横浜(横浜)
• [Presentation] インテグリン結合モチーフを含む人工設計リポペプチドはトル様受容体2のリガンドとして機能し、効果的なアジュバント活性を持っ (2009)
  • Author(s): 赤澤隆
  • Organizer: 第13回日本がん免疫学会
  • Place of Presentation: 北九州国際会議場(小倉)
• [Remarks] ホームページ等
  • URL: http://www.mc.pref.osaka.jp
• [Remarks]
  • URL: http://www.mc.pref.osaka.jp/omc2/genetics.html