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Analyses for the establishment of the effective immunotherapy to melanoma-bearing hosts

Research Project

Project/Area Number 23591613
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionUniversity of Yamanashi

Principal Investigator

SHIBAGAKI Naotaka  山梨大学, 医学工学総合研究部, 准教授 (40262662)

Co-Investigator(Kenkyū-buntansha) INOZUME Takashi  山梨大学, 医学部附属病院, 助教 (80334853)
HANAWA Fumie  山梨大学, 医学部附属病院, 助教 (80535592)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords腫瘍免疫 / 悪性黒色腫 / ワクチン / 皮膚腫瘍 / 癌免疫療法 / STAT3 / メラノーマ / がん免疫
Research Abstract

We revealed that STAT3-restricted cytokines, especially IL-6 from B16 melanoma cells suppressed IFN-gamma-production in both CD4+ and CD8+ T-cells. In culture, IL-6 from B16 cells was reduced by pretreatment with rR9-GRIM19. In vivo, although intratumoral injections of rR9-GRIM19 elicited anti-B16 effects with frequencies of IL-6-producing T-cell phenotypes, complete B16 regression was not observed. To elicit complete B16 regression, we investigated the antitumor effects of combination immunotherapies with rR9-GRIM19. rR9-GRIM19 elicited enhanced antitumor effects when combined either with rR9-OVA or CpG-ODN, but only the combination of CpG-ODN, rR9-OVA, and rR9-GRIM19 (COG therapy) elicited complete B16 tumor regression. Interestingly, melanoma-specific cytotoxic T lymphocyte (CTL) expansion with IFN production occurred in COG-treated B16-bearing. We finally confirmed that rIFN exposure could significantly enhance rR9-GRIM19-treated anti-B16 melanoma effects in vitro and in vivo.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (28 results)

All 2013 2012 2011 Other

All Journal Article (3 results) (of which Peer Reviewed: 1 results) Presentation (23 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] 腫瘍免疫療法のトピックス2012

    • Author(s)
      柴垣直孝
    • Journal Title

      Skin Cancer

      Volume: 26巻 Pages: 267-273

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Journal Article] Protein-transduction domainを用いた抗原性の増強2011

    • Author(s)
      柴垣直孝、島田眞路
    • Journal Title

      臨床免疫アレルギー科

      Volume: 55巻 Pages: 255-261

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Journal Article] Novel Immunotherapeutic approaches to skin cancer treatments using protein transduction technology2011

    • Author(s)
      NAOTAKA SHIBAGAKI
    • Journal Title

      Journal of Dermatological Science

      Volume: 61巻 Issue: 3 Pages: 153-161

    • DOI

      10.1016/j.jdermsci.2010.12.003

    • NAID

      10030890246

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] がん微小環境における免疫抑制状態の機序2013

    • Author(s)
      柴垣直孝
    • Organizer
      第29回皮膚悪性腫瘍学会総会
    • Place of Presentation
      甲府市
    • Year and Date
      2013-08-09
    • Related Report
      2013 Final Research Report
  • [Presentation] IL-6 produced from B16 melanoma cells activates STAT3 in all CD4+ and CD8+ T cells with suppressing the IFN-gamma-producing potential2013

    • Author(s)
      柴垣直孝
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      宇部市
    • Year and Date
      2013-07-04
    • Related Report
      2013 Final Research Report
  • [Presentation] 最新の皮膚医学研究;STAT3に対する新規分子標的阻害薬の開発とその抗腫瘍効果の解析2013

    • Author(s)
      柴垣直孝
    • Organizer
      第112回日本皮膚科学会総会学術大会
    • Place of Presentation
      横浜市
    • Year and Date
      2013-06-26
    • Related Report
      2013 Final Research Report
  • [Presentation] Complete B16 melanoma regression with melanoma-specific CTL expansion is elicited simply by intratumoral injections of rR9-GRIM19 plus Th1/Tc1-inducible adjuvants2013

    • Author(s)
      Naotaka Shibagaki
    • Organizer
      8^<th> World Congress of Melanoma (World melanoma 2013)
    • Place of Presentation
      ドイツハンブルグ
    • Related Report
      2013 Final Research Report
  • [Presentation] STAT3に対する新規分子標的阻害薬の開発とその抗腫瘍効果の解析2013

    • Author(s)
      柴垣直孝
    • Organizer
      第112回日本皮膚科学会総会 学術大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] IL-6 produced from B16 melanoma cells activates STAT3 in all CD4+ and CD8+ T cells with suppressing the IFN-gamma-producing potential.2013

    • Author(s)
      花輪書絵
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      ANAクラウンプラザホテル宇部(山口県宇部市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Complete B16 melanoma regression with melanoma-specific CTL expansion is elicited simply by intratumoral injections of rR9-GRIM19 plus Th1/Tc1-inducible adjuvants.2013

    • Author(s)
      Naotaka Shibagaki
    • Organizer
      8th World Congress of Melanoma (World melanoma 2013)
    • Place of Presentation
      Congress Center Hamburg(ドイツ ハンブルグ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] がん微小環境における免疫抑制状態の機序2013

    • Author(s)
      柴垣直孝
    • Organizer
      第29回皮膚悪性腫瘍学会総会
    • Place of Presentation
      甲府富士屋ホテル(山梨県甲府市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] A20 tumor regression by rR9-GRIM19 is elicited via both CD8+ and CD4+T cell conversion of IL-10 into IL-17/IFN-gamma-producing phenotypes2012

    • Author(s)
      花輪書絵、柴垣直孝
    • Organizer
      第37回日本研究皮膚科学会総会
    • Place of Presentation
      那覇市
    • Year and Date
      2012-12-08
    • Related Report
      2013 Final Research Report
  • [Presentation] B cell lymphoma regression following intratumoral injections of a novel STAT3-inhibitor (rR9-GRIM19) alone is ekicited via both CD8+ and CD4+ T cell conversion of IL-10-producing into IL-17/IFN-gamma-producing phenotypes2012

    • Author(s)
      柴垣直孝
    • Organizer
      第41回日本免疫学会総会
    • Place of Presentation
      神戸市
    • Year and Date
      2012-12-07
    • Related Report
      2013 Final Research Report
  • [Presentation] A20 tumor regression by rR9-GRIM19 is elicited via T cell conversion of IL-10 into IL-17/IFN-gamma-producing phenotypes2012

    • Author(s)
      柴垣直孝
    • Organizer
      第16回日本がん免疫学会総会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Final Research Report
  • [Presentation] Complete cutaneous B-cell lymphoma regression following intratumoral injections of a novel STAT3-inhibitor (rR9-GRIM19) alone is elicited via rapid CD8+ and CD4+ T cell conversion of IL-10-producing into IL-17/IFN-gamma-producing phenotypes2012

    • Author(s)
      柴垣直孝
    • Organizer
      第42回ヨーロッパ研究皮膚科学会総会
    • Place of Presentation
      イタリアベニス
    • Related Report
      2013 Final Research Report
  • [Presentation] A20 tumor regression by rR9-GRIM19 is elicited via T cell conversion of IL-10 into IL-17/ IFN-gamma-producing phenotypes.2012

    • Author(s)
      柴垣直孝
    • Organizer
      第16回日本がん免疫学会総会
    • Place of Presentation
      北海道大学学術交流会館(札幌)
    • Related Report
      2012 Research-status Report
  • [Presentation] Complete cutaneous B-cell lymphoma regression following intratumoral injections of a novel STAT3-inhibitor (rR9-GRIM19) alone is elicited via rapid CD8+ and CD4+ T cell conversion of IL-10-producing into IL-17/ IFN-gamma-producing phenotypes.2012

    • Author(s)
      柴垣直孝
    • Organizer
      第42回ヨーロッパ研究皮膚科学会総会
    • Place of Presentation
      Lido Casino (イタリア ベニス)
    • Related Report
      2012 Research-status Report
  • [Presentation] B-cell lymphoma regression following intratumoral injections of a novel STAT3-inhibitor (rR9-GRIM19) alone is elicited via both CD8+ and CD4+ T cell conversion of IL-10-producing into IL-17/ IFN-gamma producing phenotypes2012

    • Author(s)
      柴垣直孝
    • Organizer
      第41回日本免疫学会総会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] A20 tumor regressions by rR9-GRIM19 is elicited via both CD8+ and CD4+ T cell conversion of IL-10 into IL-17/ IFN-gamma-producing phenotypes.2012

    • Author(s)
      花輪書絵
    • Organizer
      第37回日本研究皮膚科学会総会
    • Place of Presentation
      ロワジールホテル那覇(那覇)
    • Related Report
      2012 Research-status Report
  • [Presentation] CTL-mediated complete B16-melanoma rejection was elicited only by the combination therapy with STAT3-inhibitor plus Th1-inducer stimulations2011

    • Author(s)
      花輪書絵、柴垣直孝
    • Organizer
      第36回日本研究皮膚科学会総会
    • Place of Presentation
      京都市
    • Year and Date
      2011-12-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Complete A20-tumor rejection by intratumoral injections of a novel STAT3-inhibitor (rR9-GRIM19) alone is elicited via rapid CD8+ and CD4+ T cell conversion of IL-10-producing into IL-17/IFN-gamma-producing phenotypes2011

    • Author(s)
      Naotaka Shibagaki
    • Organizer
      第15回日本がん免疫学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2011-06-30
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍免疫療法のトピックスー治療効果を向上させるためにはー2011

    • Author(s)
      柴垣直孝
    • Organizer
      第27回日本皮膚悪性腫瘍学会総会
    • Place of Presentation
      新宿
    • Year and Date
      2011-06-04
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍免疫療法のトピックス -治療効果を向上させるためには-2011

    • Author(s)
      柴垣直孝
    • Organizer
      第27回日本皮膚悪性腫瘍学会総会(招待講演)
    • Place of Presentation
      京王プラザホテル ( 東京)
    • Related Report
      2011 Research-status Report
  • [Presentation] Complete A20-tumor rejections by intratumoral.....2011

    • Author(s)
      Naotaka Shibagaki
    • Organizer
      第15回日本がん免疫学会総会
    • Place of Presentation
      千里ライフサイエンスセンター( 大阪)
    • Related Report
      2011 Research-status Report
  • [Presentation] A novel STAT3 inhibitor (rR9-GRIM19) ....2011

    • Author(s)
      Takashi Okamoto, Naotaka Shibagaki, et al.
    • Organizer
      Society for Investigative Dermatology
    • Place of Presentation
      JW Marriott Hotel (アメリカ合衆国アリゾナ州フェニックス)
    • Related Report
      2011 Research-status Report
  • [Presentation] CTL-mediated complete B16-melanoma ....2011

    • Author(s)
      Fumie Hanawa, Naotaka Shibagaki, et al.
    • Organizer
      第36回日本研究皮膚科学会総会
    • Place of Presentation
      京都国際会議場( 京都)
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://erdb.yamanashi.ac.jp/rdb/A_DispInfo.Scholar/0/7FB51F55041ACE1A.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 山梨大学医学部皮膚科ホームページ

    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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