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Development of allogeneic dendriticcell /tumor cell fusion hybrids vaccine based on MHC classI restriction

Research Project

Project/Area Number 16591316
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKobe University

Principal Investigator

KAMIGAKI Takashi  Kobe University, Hospital, Surgery, Associate Professor (20372641)

Co-Investigator(Kenkyū-buntansha) TAKASE Shiro  Kobe University Hospital, Surgery, Associate Professor (00379405)
IWATANI Yoshiteru  Kobe University Hospital, Surgery, Medical Staff (00457079)
NAKAMURA Tetsu  Kobe University Hospital, Surgary, Medical Staff (10403247)
KURODA Yoshikazu  Kobe University, Graduate school of Medical Science Surgery, Professor (70178143)
味木 徹夫  神戸大学, 大学院医学系研究科, 助手 (80379403)
川崎 健太郎  神戸大学, 医学部附属病院, 助手 (90379404)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,850,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordscolorectal cancer / dendritic cell / MHC / CTL / VK / cancer vaccine / DC / TC fusion hybrids / tumor immunoloey / アロ樹状細胞 / 腫瘍細胞・樹状細胞融合 / 抗CD25抗体 / 腫瘍予防モデル / 制御性Tリンパ球 / 細胞傷害性Tリンパ球 / CT26大腸癌細胞株 / 肺転移 / CT26大腸癌細胞 / gp70 env MuLV / Pentamer / pentamer
Research Abstract

1.Comparative analysis of antigen loading methods for denderitic cell-based vaccine for murine colon cancer models
1) Dentdritic cell / tumor cell (DC/ TC) fusion hybrids elicited the most effective anti-turnor response, as compared to other antigen-loading vaccines in animal models.
2) DC/TC fusion hybrids induced higher cytotoxic T lymphocyte (CTL) activity than other vaccines and the production of IFN-γ polarized to the Th1 cytokine responses.
2. Correlation between expression of MHC class I and that of antigen presenting machineries in gastrointestinal cancers
1) It was shown that β2-microglobulin and LMP-2 are important for the expression of MHC class I in pancreas, biliary tract, and colon cancer cell lines.
2) Transfection of the wild-type β2-microglobulin gene restored MHC class I antigen expression on the cell surface for the colon cancer cell line, which showed no MHC class I expression and lack of protein expression for β2-microglobulin.
3. Development of allogeneic DC/ TC fusion hybrids vaccine for colon cancer
1) Allogeneic DC/TC fusion hybrids induced greater anti-tumor efficacy compared to syngeneic fuson hybrids in murine colon cancer models.
2) Allogeneic DC/TC fusion hybrids elicited stronger CTL and NK activity than syngeneic DC/TC hybrids. Because it was found that allogeneic DC/TC hybrids induced the higher production of IFN-γ and the higher ratio of the Th1 to Th2 cytokine.
3) Additionally, DC/TC fusion hybrids vaccine induced CTLs specific to both endogenous and exogenous antigens in animal models.

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (30 results)

All 2007 2006 2004 Other

All Journal Article (23 results) (of which Peer Reviewed: 10 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma.2007

    • Author(s)
      Yasuda T
    • Journal Title

      Cancer Immunology, Immnunotherapy 56・7

      Pages: 1025-1036

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Antitumor effect of gemcitabine on orthotopically inoculated human gallbladder cancer cells in nude mice.2007

    • Author(s)
      Mita Y
    • Journal Title

      Ann Surg Oncol 14・4

      Pages: 1374-1380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Family history of cancer in Japanese gastric cancer patients.2007

    • Author(s)
      Kawasaki K
    • Journal Title

      Gastric Cancer 10・3

      Pages: 173-175

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/ tumor cell fusion hybrids for murine colon adenocarcinoma2007

    • Author(s)
      Takashi, Yasuda
    • Journal Title

      Cancer Immunol Immunother 56-7

      Pages: 1025-1036

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Antitumor effect of gemcitabine on orthotopically inoculated human gallbladder cancer cells in nude mice2007

    • Author(s)
      Yoshiyasu, Mita
    • Journal Title

      Ann Surg Oncol 14-4

      Pages: 1374-1380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Antitumor effect of gemcitabine on orthotopically inoculated human gallbladder cancer cells in nude mice2007

    • Author(s)
      Yoshiyasu, Mita
    • Journal Title

      Gastric Cancer 10-3

      Pages: 173-175

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma.2007

    • Author(s)
      Yasuda T
    • Journal Title

      Cancer Immunology, Immunotherapy 第56巻・第7号

      Pages: 1025-1036

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cell-tumor cell hybrids enhance the induction of cytotoxic T lymphocytes against murine colon cancer: a comparative analysis of antigen loading methods for the vaccination of immunotherapeutic dendritic cells.2006

    • Author(s)
      Yasuda T
    • Journal Title

      Oncology Report 16・6

      Pages: 1317-1324

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] MDR1 T-129C polymorphism can be predictive of differentiation, and thereby prognosis of colorectal adenocarcinomas in Japanese.2006

    • Author(s)
      Koyama T
    • Journal Title

      Biol Pharm Bull 29・7

      Pages: 1449-1453

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Thymidylate synthase and dihydropyrimidine dehydrogenase expressions in gallbladder cancer.2006

    • Author(s)
      Ajiki T
    • Journal Title

      Anticancer Res 26・2B

      Pages: 1391-1396

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Correlation between expression of major histocompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the pancreas, biliary tract and colon.2006

    • Author(s)
      Imanishi T
    • Journal Title

      Kobe Journal of Medical Science 52・3-4

      Pages: 85-95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Family history of cancer in Japanese gastric cancer natients2006

    • Author(s)
      Kentaro, Kawasaki
    • Journal Title

      Oncol Rep 18-6

      Pages: 1317-1324

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] MDRI T-129C polymorphism can be predictive of differentiation, and thereby prognosis of colorectal adenocarcinomas in Japanese2006

    • Author(s)
      Tatsuya, Koyama
    • Journal Title

      BioJ Pharm Bull 29-7

      Pages: 1449-1453

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Thymidylate synthase and dihydropyrimidine Dehydrogenase expressions in gallbladder cancer2006

    • Author(s)
      Tetsuo, Ajiki
    • Journal Title

      Anticancer Res 26-2B

      Pages: 1391-1396

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Correlation between expression of major histocompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the nancreas. biliary tract and colon2006

    • Author(s)
      Tatsuya, Imanishi
    • Journal Title

      Kobe Journal of Medical Sciences 52-3-4

      Pages: 85-95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Dendritic cell-tumor cell hybrids enhance the induction of cytotoxic Tlymphocytes against murine colon cancer : a comparative analysis of antigen loading methods for the vaccination of immunotherapeutic dendritic cells.2006

    • Author(s)
      Yasuda T
    • Journal Title

      Oncology Report 第16巻・第6号

      Pages: 1317-1324

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Correlation between expression of major histocompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the pancreas, biliary tract and colon.2006

    • Author(s)
      Imanishi T
    • Journal Title

      Kobe Journal of Medical Science 第52巻・第3-4号

      Pages: 85-95

    • Related Report
      2006 Annual Research Report
  • [Journal Article] MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas.2004

    • Author(s)
      Nishioka C
    • Journal Title

      Kobe Journal of Medical Science 50・5-6

      Pages: 181-188

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Association of VEGF genotype with mRNA level in colorectal adenocarcinomas.2004

    • Author(s)
      Yamamori M
    • Journal Title

      Biochem Biophys Res Cotmmun 323・1

      Pages: 144-150

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] MDRI, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas2004

    • Author(s)
      Chiharu, Nishioka
    • Journal Title

      Kobe Journal of Medical Sciences 50-5-6

      Pages: 181-188

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Association of VEGF genotype with mRNA level in colorectal adenocarcinomas2004

    • Author(s)
      Motohiro, Yamamori
    • Journal Title

      Biochem Biophys Res Commun 323-1

      Pages: 144-150

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma.

    • Author(s)
      Yasuda T
    • Journal Title

      Cancer Immunology, Immunotherapy (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Correlation between expression of major histcompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the pancreas, biliary tact and clolon

    • Author(s)
      Tatsuya Imanishi
    • Journal Title

      Kobe Journal of Medical Sciences (In press)

    • Related Report
      2005 Annual Research Report
  • [Presentation] 自己あるいは非自己樹状細胞と腫瘍細胞との融合細胞ワクチンの有用性に関する比較検討2006

    • Author(s)
      安田 貴志
    • Organizer
      第65回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A comparative analysis of syngeneic and allogeneic DC/ TC fusion hybrids vaccine for anti-tumor efficacy2006

    • Author(s)
      Takashi, Yasuda
    • Organizer
      The 65th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-28
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 自己あるいは非自己樹状細胞と腫瘍細胞との融合細胞ワクチンの有用性に関する比較検討2006

    • Author(s)
      安田 貴志
    • Organizer
      第61回日本消化器外科学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-07-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A comparative analysis of syngeneic and allogeneic DC/ TC fusion hybrids vaccine for anti-tumor efficacy2006

    • Author(s)
      Takashi, Yasuda
    • Organizer
      The 61st Annual Meeting of the Japanese Society of Gastroenterological Surgery
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-07-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 自己及び非自己樹状細胞と腫瘍細胞との融合細胞ワクチンによる複数のCTL誘導能に関する検討2006

    • Author(s)
      安田 貴志
    • Organizer
      第106回日本外科学会定期学術集会
    • Place of Presentation
      東京
    • Year and Date
      2006-03-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Induction of CTLs specific to different tumor antigens by syngeneic and allogeneic DC/ TC fusion hybrids vaccine2006

    • Author(s)
      Takashi, Yasuda
    • Organizer
      The 106th Annual Congress of the Japan Surgical Society
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-03-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.med.kobe-u.ac.jp/surg1/cn2/pg13.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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