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Development of the augmenting agent of cancer-specific immune responses and the inhibiter against the immune suppressive molecule for promoting cancer immunotherapy

Research Project

Project/Area Number 16H05044
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Integrative animal science
Research InstitutionOsaka Prefecture University

Principal Investigator

Sugiura Kikuya  大阪府立大学, 生命環境科学研究科, 教授 (30171143)

Co-Investigator(Kenkyū-buntansha) 藤原 大佑  大阪府立大学, 理学(系)研究科(研究院), 講師 (30611420)
鳩谷 晋吾  大阪府立大学, 生命環境科学研究科, 准教授 (40453138)
赤澤 隆  地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, がん創薬部主任研究員 (80359299)
弓場 英司  大阪府立大学, 工学(系)研究科(研究院), 准教授 (80582296)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywordsがん免疫治療 / 抗原特異的免疫増強剤 / 免疫抑制分子阻害剤 / トランスレーショナルリサーチ / がん特異的免疫増強剤 / 免疫抑制分子標的阻害剤 / 樹状細胞 / 抑制分子標的阻害剤 / 抑制性T細胞 / がん抗原特異的免疫増強剤 / 生体関連高分子化学 / 生物分子化学 / 免疫学 / 免疫増強剤 / 分子標的阻害剤
Outline of Final Research Achievements

The agent for augmenting cancer-specific immune responses was developed with the liposome conjugated with a ligand of dendritic cell (DC)-targeting toll-like receptor and a pH-sensitive polymer that enhances antigen-presentation by DC. The agent significantly enhanced cancer antigen-specific cytotoxic T cell activity, and significantly suppressed growth of cancer cells in syngeneic mice. On the other hand, the peptide targeting an immune suppressive molecule, CTLA-4 was generated against recombinant human CTLA-4-Ig by east-display and error-prone PCR methods. The targeting-peptide showed potent binding activity to canine DCs, and significantly enhanced canine T cell responses against allogeneic DCs, suggesting that the targeting peptide effectively block the binding between CTLA-4 on T cells and B7 on DCs. These agents will be promising tool for promoting therapeutic effect of cancer immunotherapy in human and veterinary medicine.

Academic Significance and Societal Importance of the Research Achievements

がん免疫治療は、患者の免疫機構を利用してがんを治療する方法で、副作用がほとんどなく安全である反面、治療効果が低いため、治癒を目的として単独で用いられることは非常に少ない。しかし、がんが死因の多くを占め、さらに増加を示す今日では、患者の身体的負担を極力軽減し、且つ効果的ながん治療法を開発することが必要であり、そのためには、がん免疫治療の効果向上が最も重要な課題である。本研究において開発したがん特異的免疫増強剤と抑制分子標的阻害剤は、非常に高い治療効果を示した。これらを臨床応用することができれば、人と動物のがん治療に大きな進展をもたらすと考える。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (35 results)

All 2020 2019 2018 2017 2016

All Journal Article (16 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 16 results,  Open Access: 14 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] An immune-stimulatory helix-loop-helix peptide: selective inhibition of CTLA-4/B7 interaction.2020

    • Author(s)
      Ramanayake Mudiyanselage TMR, Michigami M, Ye Z, Uyeda A, Inoue N, Sugiura K, Fujii I, Fujiwara D
    • Journal Title

      ACS Chem Biol

      Volume: 15 Issue: 2 Pages: 360-368

    • DOI

      10.1021/acschembio.9b00743

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Feline embryo development in commercially available human media supplemented with fetal bovine serum2019

    • Author(s)
      ALAM Md. Emtiaj、IWATA Jun、FUJIKI Kana、TSUJIMOTO Yasunori、KANEGI Ryoji、KAWATE Noritoshi、TAMADA Hiromichi、INABA Toshio、SUGIURA Kikuya、HATOYA Shingo
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 81 Issue: 4 Pages: 629-635

    • DOI

      10.1292/jvms.18-0335

    • NAID

      130007638716

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of feline embryos produced by Piezo-actuated intracytoplasmic sperm injection of elongated spermatids2019

    • Author(s)
      TSUJIMOTO Yasunori、FUJIKI Kana、ALAM MD Emtiaj、TSUKAMOTO Masaya、AZUMA Rika、KANEGI Ryoji、ANZAI Masayuki、INABA Toshio、SUGIURA Kikuya、HATOYA Shingo
    • Journal Title

      Journal of Reproduction and Development

      Volume: 65 Issue: 3 Pages: 245-250

    • DOI

      10.1262/jrd.2018-119

    • NAID

      130007662981

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical findings and treatment of disseminated ‘<i>Mycobacterium avium</i> subspecies <i>hominissuis’</i> infection in a domestic cat2019

    • Author(s)
      Kanegi R, Yasugi M, Nabetani T, Tanaka T, Wada Y, Hirai K, Sugiura K, Hatoya S
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 81 Issue: 12 Pages: 1842-1849

    • DOI

      10.1292/jvms.19-0492

    • NAID

      130007775516

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Manipulation of the tumor microenvironment by cytokine gene transfection enhances dendritic cell‐based immunotherapy2019

    • Author(s)
      Wijesekera Daluthgamage Patsy Himali、Yuba Eiji、De Silva Nadeeka Harshini、Watanabe Shun‐ichi、Tsukamoto Masaya、Ichida Chihiro、Izawa Takeshi、Itoh Kazuyuki、Kanegi Ryoji、Hatoya Shingo、Yamate Jyoji、Inaba Toshio、Sugiura Kikuya
    • Journal Title

      FASEB BioAdvances

      Volume: 2 Issue: 1 Pages: 5-17

    • DOI

      10.1096/fba.2019-00052

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a vaccine based on bacteria-mimicking tumor cells coated with novel engineered TLR2 ligands2018

    • Author(s)
      Akazawa T, Ohashi T, Wijewardana V, Sugiura K, Inoue N.
    • Journal Title

      Cancer Science

      Volume: in press Issue: 5 Pages: 1319-1329

    • DOI

      10.1111/cas.13576

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of Footprint-Free Canine Induced Pluripotent Stem Cells Using Auto-Erasable Sendai Virus Vector2018

    • Author(s)
      Tsukamoto Masaya、Nishimura Toshiya、Yodoe Kyohei、Kanegi Ryoji、Tsujimoto Yasunori、Alam Md Emtiaj、Kuramochi Mizuki、Kuwamura Mitsuru、Ohtaka Manami、Nishimura Ken、Nakanishi Mahito、Inaba Toshio、Sugiura Kikuya、Hatoya Shingo
    • Journal Title

      Stem Cells and Development

      Volume: 27 Issue: 22 Pages: 1577-1586

    • DOI

      10.1089/scd.2018.0084

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells and rat cerebellar granule neurons2018

    • Author(s)
      Masuda Kumiko、Tsutsuki Hiroyasu、Kasamatsu Shingo、Ida Tomoaki、Takata Tsuyoshi、Sugiura Kikuya、Nishida Motohiro、Watanabe Yasuo、Sawa Tomohiro、Akaike Takaaki、Ihara Hideshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 3 Pages: 2165-2170

    • DOI

      10.1016/j.bbrc.2017.12.088

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Innate immunity mediated by dendritic cells/macrophages plays a central role in the early period in tumor treatment using gene of Mycobacterium tuberculosis antigen2018

    • Author(s)
      Takahiro Ushigusa, Yoshiyuki Koyama, Tomoko Ito, Kenichi Watanabe, James K. Chambers, Aya Hasegawa, Kazuyuki Uchida, Ryoji Kanegi, Shingo Hatoya, Toshio Inaba, Kikuya Sugiura
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 80 Issue: 2 Pages: 190-196

    • DOI

      10.1292/jvms.17-0466

    • NAID

      130006339616

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Feeder-independent canine induced pluripotent stem cells maintained under serum-free conditions2017

    • Author(s)
      Nishimura T, Hatoya S, Kanegi R, Wijesekera DP, Sanno K, Tanaka E, Sugiura K, Hiromitsu Tamada NK, Imai H, Inaba T.
    • Journal Title

      Molecular Reproduction and Development

      Volume: 印刷中 Issue: 4 Pages: 329-339

    • DOI

      10.1002/mrd.22789

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of canine induced extraembryonic endoderm-like cell line that forms both extraembryonic and embryonic endoderm derivatives2017

    • Author(s)
      Nishimura T, Unezaki N, Kanegi R, Wijesekera DPH, Hatoya S, Sugiura K, Kawate N, Tamada H, Imai H, Inaba T.
    • Journal Title

      Stem Cells and Development

      Volume: 印刷中 Issue: 15 Pages: 1111-1120

    • DOI

      10.1089/scd.2017.0026

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Development of effective tumor immunotherapy using a novel dendritic cell?targeting Toll-like receptor ligand2017

    • Author(s)
      De Silva Nadeeka H.、Akazawa Takashi、Wijewardana Viskam、Inoue Norimitsu、Oyamada Maremichi、Ohta Atsuko、Tachibana Yuki、Wijesekera Daluthgamage Patsy H.、Kuwamura Mitsuru、Nishizawa Yasuko、Itoh Kazuyuki、Izawa Takeshi、Hatoya Shingo、Hasegawa Tetsuya、Yamate Jyoji、Inaba Toshio、Sugiura Kikuya
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 11 Pages: 0188738-0188738

    • DOI

      10.1371/journal.pone.0188738

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of pH-sensitive Dextran Derivatives with Strong Adjuvant Function and Their Application to Antigen Delivery2017

    • Author(s)
      Yuba Eiji、Uesugi Shinya、Miyazaki Maiko、Kado Yuna、Harada Atsushi、Kono Kenji
    • Journal Title

      Membranes

      Volume: 7 Issue: 3 Pages: 41-41

    • DOI

      10.3390/membranes7030041

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity2017

    • Author(s)
      E. Yuba, N. Sakaguchi, Y. Kanda, M. Miyazaki, K. Koiwai
    • Journal Title

      Vaccines

      Volume: 5 Issue: 4 Pages: 41-41

    • DOI

      10.3390/vaccines5040041

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of feline leukemia inhibitory factor with biological activity in Escherichia coli.2016

    • Author(s)
      Kanegi R, Hatoya S, Tsujimoto Y, Takenaka S, Nishimura T, Wijewardana V, Sugiura K, Takahashi M, Kawate N, Tamada H, Inaba T.
    • Journal Title

      Theriogenology

      Volume: 印刷中 Issue: 2 Pages: 604-611

    • DOI

      10.1016/j.theriogenology.2016.02.013

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exosomes derived from tumor cells genetically modified to express Mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy.2016

    • Author(s)
      Koyama Y, Ito T, Hasegawa A, Eriguchi M, Inaba T, Ushigusa T, Sugiura K.
    • Journal Title

      Biotechnol Lett

      Volume: 38 Issue: 11 Pages: 1857-1866

    • DOI

      10.1007/s10529-016-2185-1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腫瘍微小環境へのサイトカイン遺伝子の導入操作による樹状細胞療法の増強2020

    • Author(s)
      上垣まい、渡邊駿一、弓場英司、鳩谷晋吾、杉浦喜久弥
    • Organizer
      日本獣医再生医療学会第
    • Related Report
      2019 Annual Research Report
  • [Presentation] 結核菌抗原を「人工ネオアンティジェン」として提示したエクソソームによる腫瘍治療効果の検討2019

    • Author(s)
      杉浦喜久弥、小山義之、伊藤智子、長谷川綾、大内若菜、江里口正純、稲葉俊夫
    • Organizer
      第14回獣医再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 結核菌抗原を「人工ネオアンティジェン」として提示したエクソソームによる抗腫瘍免疫活性化のメカニズム2019

    • Author(s)
      小山義之、伊藤智子、長谷川綾、大内若菜、稲葉俊夫、江里口正純、杉浦喜久弥
    • Organizer
      第16回日本免疫治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高効率アジュバントを用いた腫瘍免疫治療の検討2018

    • Author(s)
      柿原優佳、弓場英司、Nadeeka De Silva H、赤澤隆、井上徳光、金城綾二、鳩谷普吾、稲葉俊夫、杉浦喜久弥
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ESAT-6 DNA導入による腫瘍治療効果の免疫組織化学的解析2018

    • Author(s)
      大内若菜、牛草貴博、小山義之、伊藤智子、渡辺謙一、CHAMBERS Jamew K、内田和幸、金城綾二、鳩谷普吾、稲葉俊夫、杉浦喜久弥
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development competence of domestic cat oocytes from ovaries stored at various durations at 4 C in different solution.2018

    • Author(s)
      MD EMTIAJ ALAM、花房佳祐、鳩谷晋吾、辻本恭典、稲葉俊夫、杉浦喜久弥
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 治療や病因解明への応用可能なイヌiPS細胞の作製2018

    • Author(s)
      塚本雅也、西村俊哉、金城稜二、倉持瑞樹、桑村充、大高真奈美、西村健。中西真人、稲葉俊夫、杉浦喜久弥、鳩谷晋吾
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Isolation and Qualification of Canine and Feline Mesenchymal Stem Cells by Monitoring of Glutathione Levels2018

    • Author(s)
      Kosuke Mitani, Yuki Ito, Yukio Takene, Eui Man Jeong, Heun-Soo Kang, In-Gyu Kim, Toshio Inaba, Shingo Hatoya, Kikuya Sugiura
    • Organizer
      第5回国際組織工学・再生医療学会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Generation of Helix-Loop-Helix peptide inhibitor of the interaction between human -CTLA-4 and B72018

    • Author(s)
      R.M.T.M. Ramanayake, D. Fujiwara, M. Michigam, K. Sugiura, I. Fujii
    • Organizer
      第10回国際ペプチドシンポジウム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] がん免疫治療の強化を目的とした遺伝子治療2017

    • Author(s)
      杉浦喜久弥
    • Organizer
      第12回日本獣医再生医療学会
    • Place of Presentation
      名古屋プライムセントラルタワー(愛知県名古屋市)
    • Year and Date
      2017-02-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] サイトカイン遺伝子導入による内臓転移腫瘍に対する治療効果の検討2017

    • Author(s)
      高木彩夏、Nadeeka De Silva、弓場英司、Wijesekera H Daluthgamage Patsy、鳩谷普吾、金城綾二、稲葉俊夫、杉浦喜久弥
    • Organizer
      第160回日本獣医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Manipulation of tumor microenvironment by cytokine gene transfection enhances dendritic cell-based immunotherapy2017

    • Author(s)
      Kikuya Sugiura, Daluthgamage Patsy Himali Wijesekera, Eiji Yuba, Nadeeka Harshini De Silva, Shingo Hatoya, Tosho Inaba
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] pH-sensitive polysaccharides-based immunity-inducing systems2017

    • Author(s)
      E. Yuba, A. Yamaguchi, A. Harada, K. Kono
    • Organizer
      第66回高分子学会年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] pH応答性多糖修飾リポソームの抗原ペプチドデリバリーキャリアとしての機能2017

    • Author(s)
      弓場英司,能﨑優太,原田敦史,宇高恵子,西村泰治,河野健司
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 結核菌抗原遺伝子を用いた腫瘍治療メカニズムも解明2016

    • Author(s)
      長谷川綾,牛草貴博,小山義之,伊藤智子,鳩谷晋吾,杉浦喜久弥,稲葉俊夫
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学生命資源科学部(神奈川県藤沢市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] イヌ体細胞を用いた人口誘導胚体外内胚葉の作製と肝細胞への分化誘2016

    • Author(s)
      畦崎直哉,西村俊哉,金城綾二,Himali Wijesekera,鳩谷晋吾,杉浦喜久弥,川手憲俊,玉田尋通,今井裕,稲葉俊夫
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学生命資源科学部(神奈川県藤沢市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] ネコ」iPS細胞株のセンダイウイルスベクターを用いた作製2016

    • Author(s)
      沖田良太,鳩谷晋吾,杉浦喜久弥,大高真奈美,西村建,中西真人,稲葉俊夫
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学生命資源科学部(神奈川県藤沢市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Manipulation of tumor microenvironment by cytokine gene transfection enhances dendritic cell-based immunotherapy2016

    • Author(s)
      Sugiura K, Wijesekera DPH, Ichida C, Yuba E, Kono K, Yamate J, Kanegi R, Nishimura T, De Silva N, Hatoya Y, Inaba T
    • Organizer
      第17回国際免疫学会
    • Place of Presentation
      Melbourune,Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗腫瘍免疫反応を増強した樹状細胞療法の開発の試み2016

    • Author(s)
      杉浦喜久弥
    • Organizer
      2016年日本獣医臨床病理学会
    • Place of Presentation
      日本獣医生命科学大学(東京都武蔵野市)
    • Year and Date
      2016-05-28
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2023-01-30  

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