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Manipulation of tumor microenvironment by cytokine gene transfection enhances dendritic cell-based immunotherapy

Research Project

Project/Area Number 23380174
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(系), 准教授 (30171143)

Co-Investigator(Kenkyū-buntansha) 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、腫瘍免疫部門, 主任研究員 (80359299)
HATOYA Shingo  大阪府立大学, 生命環境科学研究科, 准教授 (40453138)
INABA Toshio  大阪府立大学, 生命環境科学研究科, 教授 (00137241)
稲葉 宗夫  関西医科大学, 医学部, 准教授 (70115947)
Co-Investigator(Renkei-kenkyūsha) KOUNO Kenji  大阪府立大学, 工学研究科, 教授 (90215187)
Project Period (FY) 2011-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywords腫瘍免疫治療 / 遺伝子導入 / 人工ベクター / DC40リガンド / インターフェロンγ / 樹状細胞 / がん免疫治療 / CD40リガンド / pH感受性リポソーム / トル様レセプターリガンド / 腫瘍微小環境 / 合成ベクター / がん治療 / トル様受容体リガンド / シクロオキシゲナーゼ阻害薬 / 癌免疫治療
Outline of Final Research Achievements

Using a novel synthetic vector of a cationic lipid bound with pH-sensitive liposomes, we transfected cytokine genes into tumor cells to manipulate tumor microenvironment for facilitating dendritic cell (DC) therapy. The efficiency of transfection into the LM8 osteosarcoma growing in syngeneic C3H mice was about 10% by both intratumor (i.t.) and intravenous (i.v.) injection of the vector enclosing GFP-expression plasmid. Therapeutic experiments were performed to inhibit LM8 growth by injection of the interferon (IFN) γ-vector or the CD40L-vector, followed by i.t. injection of the DCs presenting the LM8 antigens. Growth of the tumor was significantly suppressed by the treatment of the IFNγ-plasmid vector and the CD40L-plasmid vector. The CD40L-vector treatment led to significantly improved survival. These results indicate that gene transfection of the cytokine genes manipulate the tumor microenvironment effectively and significantly improve DC-based tumor immunotherapy.

Report

(6 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (28 results)

All 2016 2015 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (11 results) (of which Invited: 4 results) Remarks (1 results)

  • [Journal Article] Highly effective non-viral antitumor gene therapy system comprised of biocompatible small plasmid complex particles consisting of pDNA, anionic polysaccharide, and fully deprotected linear polyethylenimine2015

    • Author(s)
      Yoshiyuki Koyama, Kikuya Sugiura, Chieko Yoshihara, Toshio Inaba, Tomoko Ito
    • Journal Title

      Pharmaceutics

      Volume: 7 Issue: 3 Pages: 152-164

    • DOI

      10.3390/pharmaceutics7030152

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of ovarian hormones on maturation of dendritic cells from peripheral blood monocytes in dogs2015

    • Author(s)
      Wijewardana V, Sugiura K, Wijesekera DPH, Hatoya S, Nishimura T, Kanegi R, Ushigusa T, Inaba T.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 77 Issue: 7 Pages: 771-775

    • DOI

      10.1292/jvms.14-0558

    • NAID

      130005089954

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] pH-Sensitive polymer-liposome-based antigen delivery systems potentiated with interferon-γ gene lipoplex for efficient cancer immunotherapy2015

    • Author(s)
      E. Yuba, Y. Kanda, Y. Yoshizaki, R. Teranishi, A. Harada, K. Sugiura, T. Izawa, J. Yamate, N. Sakaguchi, K. Koiwai, K. Kono,
    • Journal Title

      Biomaterials

      Volume: 67 Pages: 214-224

    • DOI

      10.1016/j.biomaterials.2015.07.031

    • NAID

      120007159642

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effective enhancement of anti-tumor immune responses by transfection of IFNγ gene into tumor using a new type synthetic vector.2014

    • Author(s)
      Wijesekera, D.P.H., Sugiura, K., Yuba, E., Ueda, K., Wijewardana, V., Kanegi, R., Nishimura, T., Ushigusa, T., Hatoya, S., Kono, K., Inaba, T.
    • Journal Title

      Vet. Immunol. Immunopathol.

      Volume: 162 Issue: 1-2 Pages: 59-64

    • DOI

      10.1016/j.vetimm.2014.08.016

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evaluation of serum phosphotylated neurofilament subunit NF-H as a prognostic biomarker in dogs with thoracolumbar intervertebral disc herniation.2014

    • Author(s)
      Nishida H, Nakayama M, Tanaka H, Kamishima H, Izawa T, Hatoya S, Sugiura K, Ide C, Inaba T
    • Journal Title

      Vet. Surg.

      Volume: 43 Issue: 3 Pages: 289-293

    • DOI

      10.1111/j.1532-950x.2014.12144.x

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of functional platelets from canine induced pluripotent stem cells.2013

    • Author(s)
      Nishimura, T., Hatoya, S., Kanegi, R., Sugiura, K., Wijewardana, V., Kuwamura, M., Tanaka, M., Yamate, J., Izawa, T., Takahashi, M., Kawate, N., Tamada, H., Imai, H., Inaba, T.
    • Journal Title

      Stem Cells Dev.

      Volume: 22 Issue: 14 Pages: 2026-2035

    • DOI

      10.1089/scd.2012.0701

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 樹状細胞とインターフェロン-γを併用したイヌ腫瘍に対する治療効果2013

    • Author(s)
      杉浦喜久弥
    • Journal Title

      InfoVets

      Volume: 16 Pages: 17-24

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Three cases of idiopathic sterile pyogranulomatous inflammation of epidural fat in Miniature Dachshunds.2012

    • Author(s)
      Nishida H, Tanaka H, Kitamura M, Hatoya S, Sugiura K, Inaba T, Nakayama M.
    • Journal Title

      J Vet Med Sci

      Volume: 74 Pages: 1071-1074

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of methods for cell harvesting and the biological properties at successive passages of canine bone marrow stromal cells.2012

    • Author(s)
      Nishida Hidetaka
    • Journal Title

      American journal of veterinary research

      Volume: 3 Issue: 11 Pages: 1832-1840

    • DOI

      10.2460/ajvr.73.11.1832

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safety of autologous bone marrow stromal cell transplantation in dogs with acute spinal cord injury.2012

    • Author(s)
      Nishida H, Nakayama M, Tanaka H, Kitamura M, Hatoya S, Sugiura K, Harada Y, Suzuki Y, Ide C, Inaba T
    • Journal Title

      Vet. Surg.

      Volume: 41 Pages: 437-442

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大阪における犬猫からのメチシリン耐性ブドウ球菌の検出状況と薬剤感受性2012

    • Author(s)
      鳩谷晋吾、古家優、秋吉秀保、谷浩行、島田恵理子、宮本忠、杉浦喜久弥、稲葉俊夫
    • Journal Title

      動物臨床医学

      Volume: 21 Pages: 175-178

    • NAID

      10031143103

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methods for cell harvesting and the biological properties of canine bone marrow stromal cells at successive passages2012

    • Author(s)
      Nishida H, Shoji Y, Nakamura M, Hatoya S, Sugiura K, Yamate J, Kuwamura M, Kotani T, Nakayama M, Suzuki Y, Ide C, Inaba T
    • Journal Title

      Am. J. Vet. Res

      Volume: (印刷中) Issue: 8 Pages: 1118-1123

    • DOI

      10.2460/ajvr.72.8.1118

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful management with CHOP for pulmonary lymphomatoid granulomatosis in a dog.2011

    • Author(s)
      Hatoya S. et al.
    • Journal Title

      J. Vet. Med. Sci.

      Volume: 73 Pages: 527-530

    • NAID

      130000444583

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of fertile oestrus in dioestrous bitches by prostaglandin F2α and a GnRH-agonist2011

    • Author(s)
      Ohmura M, Torii R, Hatoya S, Sugiura K, Tamada H, Kawate N, Takahashi M, Sawada T, Inaba T
    • Journal Title

      Vet. Rec

      Volume: 168巻 Issue: 25 Pages: 669-669

    • DOI

      10.1136/vr.d1183

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] サイトカイン遺伝子治療と樹状細胞療法の併用によるがん免疫治療2016

    • Author(s)
      杉浦喜久弥
    • Organizer
      平成27年度獣医学術学会年次大会
    • Place of Presentation
      秋田キャッスルホテル(秋田県秋田市)
    • Year and Date
      2016-02-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] コンパニオンアニマルのガン免疫療法2016

    • Author(s)
      杉浦喜久弥
    • Organizer
      第5回バイオ・メディカル・フォーラム/第2回産学連携ヘルスケアナレッジセミナー
    • Place of Presentation
      大阪府立大学(大阪府堺市)
    • Year and Date
      2016-02-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 免疫療法(療法原理の基礎、基礎研究、臨床応用)2016

    • Author(s)
      杉浦喜久弥
    • Organizer
      日本獣医再生医療学会
    • Place of Presentation
      ホテルクライトン新大阪(大阪府大阪市)
    • Year and Date
      2016-02-06
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Effect of ovarian hormones on maturation of dendritic cells from peripheral blood monocytes in dogs2015

    • Author(s)
      De Silva H. Nadeeka, Sugiura Kikuya, Wijesekera H. Daluthgamage Pasty, Hatoya Shingo, Inaba Toshio
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Manipulation of tumor microenvironment by cytokine gene transfection enhances dendritic cell-based immunotherap2015

    • Author(s)
      Wijesekera H. Daluthgamage Pasty, Sugiura Kikuya, Hatoya Shingo, Inaba Toshio
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] サイトカイン遺伝子治療と樹状細胞療法の併用によるがん免疫治療2015

    • Author(s)
      市田千尋、杉浦喜久弥、Wijesekera H Daluthgamage Patsy、弓場英司、鳩谷晋吾、河野健司、稲葉俊夫
    • Organizer
      第158回日本獣医学会学術集会
    • Place of Presentation
      北里大学(青森県十和田)
    • Year and Date
      2015-09-07
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウス内臓転移モデルにおける免疫応答反応を増強した樹状細胞治療法の治療効果の検討2014

    • Author(s)
      太田敦子、杉浦喜久弥、赤澤隆、Wijewardana Viskam、Wijesekera H Dalthgamage Pathy、今本成樹、鳩谷晋吾、井上徳光、稲葉俊夫
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2014-09-09 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 全身的抗腫瘍免疫反応を増強した樹状細胞療法の改善2013

    • Author(s)
      東彩夏、杉浦喜久弥、立花夕季、赤澤隆、今本茂樹、Wijesekera DPH、Wijewardana V、鳩谷晋吾、井上徳光、稲葉俊夫
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Improvement of dendritic cell-based immunotherapy for enhancing systemic immune responses against cancer.2013

    • Author(s)
      Wijewardana V, Sugiura K, Akazawa T, Wijesekera DP, Imamoto S, Inoue N, Inaba T
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      千葉
    • Related Report
      2013 Annual Research Report
  • [Presentation] イヌ顆粒球減少症の治療に向けたイヌ造血因子の作製2011

    • Author(s)
      水野亜優美 他
    • Organizer
      第152回日本獣医学会学術集会
    • Place of Presentation
      大阪府堺市
    • Related Report
      2011 Annual Research Report
  • [Presentation] 樹状細胞による癌免疫療法

    • Author(s)
      杉浦喜久弥
    • Organizer
      平成25年度獣医学術学会年次大会
    • Place of Presentation
      千葉
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks] 研究内容紹介

    • URL

      http://www.vet.osakafu-u.ac.jp/profile/sugiura.html

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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