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Development of designed TLR2 ligand as antitumor immunoadjuvant

Research Project

Project/Area Number 24590500
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionResearch Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses

Principal Investigator

Takashi Akazawa  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), その他部局等, 主任研究員 (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, 部門長(腫瘍免疫学部門) (80252708)
SUGIURA Kikuya  大阪府立大学, 生命環境科学研究科, 准教授 (30171143)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords腫瘍免疫 / アジュバント / ワクチン / 人工設計 / Toll-like receptor / 癌 / 免疫 / リポペプチド / toll-like receptor / 薬学 / 免疫学 / TLR
Outline of Final Research Achievements

We have developed adjuvant engineering strategy to design the TLR2 ligand with new ability by replacing the peptide of bacterial origin with a functional motif. We designed a new dendritic cell (DC)-targeting lipopeptide, h11c (P2C-ATPEDNGRSFS), which uses the CD11c-binding sequence of ICAM-1 to selectively and efficiently activate DCs but not other immune cells. Although P2C-SKKKK is well known as artificial lipopeptide and has strong immunostimulatory activity, h11c induces stronger antitumor activity at low doses without local inflammation at vaccination site of skin. The h11c is the ideal antitumor immunoadjuvant that improvement of the efficiency and the evasion of the adverse effects were realized by functional design.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2015 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Remarks (3 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] PolyI:C-induced, TLR3/RIP3-Dependent Necroptosis Backs Up Immune Effector-Mediated Tumor Elimination In Vivo2015

    • Author(s)
      Ryo Takemura, Hiromi Takaki, Seiji Okada, Hiroaki Shime, Takashi Akazawa, Hiroyuki Oshiumi, Misako Matsumoto, Takanori Teshima, and Tsukasa Seya
    • Journal Title

      Cancer Immunology Research

      Volume: 3 Issue: 8 Pages: 902-914

    • DOI

      10.1158/2326-6066.cir-14-0219

    • NAID

      120005820710

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] PolyI:C-induced, TLR3/RIP3-dependent necroptosis backs up immune effector-mediated tumor elimination in vivo.2015

    • Author(s)
      Takemura R, Takaki H, Okada S, Shime H, Akazawa T, Oshiumi H, Matsumoto M, Teshima T, Seya T.
    • Journal Title

      Cancer Immunol Res

      Volume: -

    • NAID

      120005820710

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a dendritic cell-targeting lipopeptide as an immunoadjuvant that inhibits tumor growth without inducing local inflammation.2014

    • Author(s)
      Akazawa T, Ohashi T, Nakajima H, Nishizawa Y, Kodama K, Sugiura K, Inaba T, Inoue N.
    • Journal Title

      Int. J. Cancer.

      Volume: 135 Issue: 12 Pages: 2847-2856

    • DOI

      10.1002/ijc.28939

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A possible abscopal effect of post-irradiation immunotherapy in two patients with metastatic lung tumors.2014

    • Author(s)
      4.Kodama, K., Higashiyama, M., Okami, J., Tokunaga, T., Fujiwara, A., Inoue, N., Akazawa, T. and Seya, T.
    • Journal Title

      In. Canc. Conf. J.

      Volume: 3 Issue: 2 Pages: 122-127

    • DOI

      10.1007/s13691-013-0130-x

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of canine soluble CD40 ligand to induce maturation of monocyte derived dendritic cells for cancer immunotherapy.2013

    • Author(s)
      Wijewardana, V., Sugiura, K., Yahata, M., Akazawa, T., Wijesekera, D. P., Imamoto, S., Hatoya, S., Inoue, N., Inaba, T.
    • Journal Title

      Vet. Immunol. Immunopathol.

      Volume: 156 Issue: 1-2 Pages: 121-127

    • DOI

      10.1016/j.vetimm.2013.09.016

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dichroloacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity2013

    • Author(s)
      Ohashi, T., Akazawa, T., Aoki, M., Kuze, B., Mizuta, K., Ito, Y., Inoue, N.
    • Journal Title

      Int. J. Cancer

      Volume: 133 Issue: 5 Pages: 1107-1118

    • DOI

      10.1002/ijc.28114

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Development of bacteria-mimicked tumor cell vaccine modified with engineered TLR2 ligands2015

    • Author(s)
      Takashi Akazawa and Norimitsu Inoue
    • Organizer
      International Conference of Cancer Immunotherapy and Macrophage 2015(第19回日本がん免疫学会)
    • Place of Presentation
      東京
    • Year and Date
      2015-07-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Modification of tumor cells with bacterial components and application to vaccine.2014

    • Author(s)
      Akazawa T, Inoue N
    • Organizer
      The 73rd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] アジュバントの人工設計:樹状細胞標的化リポペプチドは局所炎症を起こさない理想的なアジュバントとして働く2013

    • Author(s)
      赤澤 隆、大橋 敏充、井上 徳光
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] CR4サブユニットを標的とした抗がん免疫アジュバント2013

    • Author(s)
      赤澤 隆、井上徳光
    • Organizer
      第50回補体シンポジウム
    • Place of Presentation
      旭川
    • Related Report
      2013 Research-status Report
  • [Presentation] Improvement of dendritic cell-based immunotherapy for enhancing systemic immune responses against cancer2013

    • Author(s)
      Viskam Wijewardana, Kikuya Sugiura, Takashi Akazawa, Dalthgamage-Pathy Wijesekera, Shigeki Imamoto, Norimitu Inoue, Toshio Inaba
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] 免疫細胞標的化トル様受容体2リガンドの人工設計と抗がんアジュバントへの応用2012

    • Author(s)
      赤澤 隆、大橋 敏充、井上 徳光
    • Organizer
      日本がん免疫学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Adjuvant engineering for caner immunotherapy: Improved synthetic TLR2 ligand with DC targeting ability2012

    • Author(s)
      Takashi Akazawa, Toshimitu Ohashi, Norimitsu Inoue
    • Organizer
      日本癌学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Remarks] 大阪府立成人病センター 研究所 腫瘍免疫学部門

    • URL

      http://www.mc.pref.osaka.jp/laboratory/department/shuyou/

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Remarks] 大阪府立成人病センター 研究所 分子遺伝学部門

    • URL

      http://www.mc.pref.osaka.jp/omc2/category/genetics.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 大阪府立成人病センター・研究所・分子遺伝学部門

    • URL

      http://www.mc.pref.osaka.jp/omc2/genetics.html

    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 新規人工設計リポペプチド2014

    • Inventor(s)
      赤澤 隆,井上 徳光
    • Industrial Property Rights Holder
      地方独立行政法人 大阪府立病院機構
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-508043
    • Filing Date
      2014-09-12
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 新規人工設計リポペプチド2013

    • Inventor(s)
      赤澤 隆、井上 徳光
    • Industrial Property Rights Holder
      地方独立行政法人大阪府立病院機構
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-03-28
    • Acquisition Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規人工設計リポペプチド2013

    • Inventor(s)
      赤澤 隆、井上 徳光
    • Industrial Property Rights Holder
      地方独立行政法人大阪府立病院機構
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-03-28
    • Related Report
      2012 Research-status Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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