Development of a useful tool adding a microbial component to tumor cell as vaccine adjuvant

2010 Fiscal Year Final Research Report

• Project/Area Number: 20200075
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology; Biological pharmacy
• Research Institution: Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
• Principal Investigator: AKAZAWA Takashi 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 研究員 (80359299)
• Co-Investigator(Renkei-kenkyūsha): INOUE Norimitsu 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 部長 (80252708)
• Project Period (FY): 2008 – 2010
• Keywords: 腫瘍 / アジュバント / ワクチン

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 our novel drug design strategy. We succeeded in development of useful synthetic adjuvants through the evaluation of new TLR2 ligands with additional functions such as targeting ability to immune cells or modification ability to tumor cells.

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. Volume: 13(4) Pages: 350-8
  • 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. Volume: 23(1) Pages: 29-41
  • Peer Reviewed
• [Journal Article] IFN-gamma markedly cooperates with intratumoral dendritic cell vaccine in dog tumormodels (2010)
  • Author(s): Mito K, Sugiura K, Ueda K,Hori T, Akazawa T, Yamate J, Nakagawa H, Hatoya S, Inaba M, Inoue N, IkeharaS, Inaba T.
  • Journal Title: Cancer Res. Volume: 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. Volume: 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. Volume: 101(7) Pages: 1596-603
  • Peer Reviewed
• [Journal Article] Two-step colocalization of MORC3 with PML nuclear bodies (2010)
  • Author(s): Mimura Y, Takahashi K, Kawata K, Akazawa T,Inoue N.
  • Journal Title: J Cell Sci. Volume: 123(Pt12) Pages: 2014-241
  • 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. Volume: 100(8) Pages: 1494-501
  • Peer Reviewed
• [Journal Article] Innate immune therapy with a Bacillus Calmette-Guerin cell wall skeleton after radical surgery for non-small cell lung cancer: a case-control study (2009)
  • Author(s): Kodama K, Higashiyama M, TakamiK, Oda K, Okami J, Maeda J, Akazawa T, Matsumoto M, Seya T, Wada M, Toyoshima K.
  • Journal Title: Surg Today. Volume: 39(3) Pages: 194-200
  • Peer Reviewed
• [Journal Article] Construction of an expression vector for improved secretion of canine IL-18 (2008)
  • Author(s): Sugiura K, Akazawa T, Fujimoto M, Wijewardana V, Mito K, Hatoya S, Taketani S, Komori M, Inoue N, Inaba T.
  • Journal Title: Vet Immunol Immunopathol. Volume: 126(3-4) Pages: 388-91
  • Peer Reviewed
• [Journal Article] Tumor-secreted lactic acid promotes IL-23/1L-17 proinflammatory pathway (2008)
  • Author(s): Shime H, Yabu M, Akazawa T, Kodama K, Matsumoto M, Seya T, Inoue N.
  • Journal Title: J Immunol. Volume: 180(11) Pages: 7175-83
  • 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: 第5回国際ペプチドシンポジウム(ポスター)
  • Place of Presentation: 京都
  • Year and Date: 20101204-09
• [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
  • Year and Date: 20100922-24
• [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
  • Year and Date: 20100822-27
• [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
  • Year and Date: 20091001-03
• [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
  • Year and Date: 20090624-25
• [Presentation] Development of designed synthetic adjuvants based on structures of toll-like receptor ligands (2008)
  • Author(s): Akazawa T, Inoue N, Matsumoto M, Seya T.
  • Organizer: 第67回日本癌学会学術総会(ポスター)
  • Place of Presentation: 名古屋
  • Year and Date: 20081028-30
• [Remarks] 地方独立行政法人大阪府立病院機構大阪府立成人病センター
  • URL: http://www.mc.pref.osaka.jp
• [Remarks] 研究所
  • URL: http://www.mc.pref.osaka.jp/omc2/top.html
• [Remarks] 分子遺伝学部門
  • URL: http://www.mc.pref.osaka.jp/omc2/genetics.html