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2011 Fiscal Year Final Research Report

Development of"immunostimulatory virotherapy"to treat various malignancies

Research Project

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Project/Area Number 21390364
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKyushu University

Principal Investigator

YONEMITSU Yoshikazu  九州大学, 薬学研究院, 教授 (40315065)

Co-Investigator(Kenkyū-buntansha) UEDA Yasuji  千葉大学, 医学研究院, 客員准教授 (80165662)
Co-Investigator(Renkei-kenkyūsha) MAEHARA Yoshihiko  九州大学, 医学研究院, 教授 (80165662)
Project Period (FY) 2009 – 2011
Keywords実験外科学
Research Abstract

Though DC-based cancer immunotherapy has been suggested as a potential treatment for various kinds of malignancies, its clinical efficacies are still insufficient in many human trials. Especially, malignant ascites(MA) is a highly intractable and immunotherapy-resistant state of advanced gastrointestinal and ovarian cancers.
First, floating cultivation of mononuclear cells from cancer patients under an optimized cytokine cocktail(GM-CSF/SCF) led these cells to stable proliferation and to DC differentiation. As are seen in conventional DCs, expanded DCs showed dendrites after maturation, and endocytotic activities. Expanded DCs also expressed HLA-DR, adhesion molecules, and co-stimulatory molecules and produced inflammatory cytokines as well as conventional DCs did. Functionally, MLR assay revealed that expanded DCs could stimulate allogenic T-cell proliferation to the same extent as conventional DCs.
Next, using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A and its decoy receptor, soluble fms-like tryrosine kinase receptor-1(sFLT-1), was a major cause of MA resistance to DC-based immunotherapy. We found that the ratio of VEGF-A/sFLT-1 was increased not only in murine but also in human MA, and F-gene. deleted recombinant Sendai virus(rSeV/dF)-mediated secretion of human sFLT-1 by DCs augmented not only the activity of DCs themselves, but also dramatically improved the survival of tumor-bearing animals associated with enhanced CTL activity and its infiltration to peritoneal tumors.

Research Products

(7 results)

All 2011 2010 Other

All Journal Article Presentation Patent(Industrial Property Rights)

  • [Journal Article] Cytokine-based high log-scale expansion of functional human dendritic cells from cord-blood CD34-positive cells2011

    • Author(s)
      Harada Y, Okada-Nakanishi Y, Ueda Y, Tsujitani S, Saito S, Fuji-Ogawa T, Iida A, Hasegawa M, Ichikawa T, Yonemitsu Y
    • Journal Title

      Sci. Rep.

      Volume: 1 Pages: 174

    • DOI

      DOI:10.1038/srep00174,2011

  • [Journal Article] Antagonism of VEGF by genetically engineered dendritic cells is essential to induce antitumor immunity against malignant ascites2011

    • Author(s)
      Sugiyama M, Kakeji Y, Tsujitani S, Harada Y, Onimaru M, Yoshida K, Tanaka S, Emi Y, Morita M, Morodomi Y, Hasegawa M, Maehara Y, Yonemitsu Y.
    • Journal Title

      Mol Cancer Ther

      Volume: 10 Pages: 540-549

  • [Journal Article] immunotherapy against various malignancies2011

    • Author(s)
      Harada Y, Yonemitsu Y
    • Journal Title

      Front Biosci

      Volume: 17 Pages: 2233-2242

  • [Presentation] Cytokine-based log-scale expansion of functional human dendritic cells from PBMC The 2nd Meeting of ACTO2011

    • Author(s)
      Harada Y, Saito S, Yonemitsu Y.
    • Organizer
      011第2回アジア細胞治療学会
    • Place of Presentation
      宮崎
    • Year and Date
      20110000
  • [Presentation] Cytokine-based log-scale expansion of functional human dendritic cells The 11th International Symposium on Dendritic Cells2010

    • Author(s)
      Harada Y, Saito S, Yonemitsu Y
    • Organizer
      第11回国際樹状細胞シンポジウム
    • Place of Presentation
      スイス
    • Year and Date
      20100000
  • [Presentation] Cytokine-based log-scale expansion of functional human dendritic cells from PBMCs American society of Gene and Cell Therapy 14th Annual meeting

    • Author(s)
      Harada Y, Saito S, Yonemitsu Y
    • Organizer
      第14回アメリカ遺伝子・細胞治療学会
    • Place of Presentation
      Seattle
  • [Patent(Industrial Property Rights)] 樹状細胞の培養方法2010

    • Inventor(s)
      原田結、齊藤智、吉田久美、米満吉和、矢崎雄一郎、岡本正人、遊佐精一
    • Industrial Property Rights Holder
      九州大学、テラ株式会社
    • Industrial Property Number
      公開特許公報(A) 、特願2010-112588、特開2011-239701
    • Filing Date
      2010-05-14

URL: 

Published: 2013-07-31  

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