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Development of cancer vaccine therapy using dendritic cells transduced with TGF-βsiRNA for digestive cancer

Research Project

Project/Area Number 20591533
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKAMURA Masaki  和歌山県立医科大学, 医学部, 助教 (80364090)

Co-Investigator(Kenkyū-buntansha) YAMAUE Hiroki  和歌山県立医科大学, 医学部, 教授 (20191190)
IWAHASHI Makoto  和歌山県立医科大学, 医学部, 講師 (70244738)
NAKAMORI Mikihito  和歌山県立医科大学, 医学部, 講師 (10322372)
MATSUDA Kenji  和歌山県立医科大学, 医学部, 助教 (30398458)
NAKA Teiji  和歌山県立医科大学, 医学部, 学内助教 (00453184)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords樹状細胞 / TGF-β / adenovirus vector / siRNA / 免疫遺伝子治療
Research Abstract

Recently, several studies have shown that TGF-βproduced from tumor cells would inhibit cytotoxic activity of cytotoxic T lymphocytes(CTLs) and increase the number of regulatory T cells(Treg) in tumor local environment. Therefore, as administration of TGF-βsiRNA would inhibit production of TGF-βin tumor environment, it would be expect that antitumor effect of immunotherapy using dendritic cells(DCs) could be enhanced. This study was examined whether antigen-specific CTL responses and therapeutic immunity could be enhanced by genetically-modified DCs expressing CEA antigen and TGF-βsiRNA. Consequently, an effective antitumor immune response was not induced because of unstable expression of TGF-βsiRNA. Further investigation is needed to optimize this vaccine therapy to achieve the obvious benefit in clinical application.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2011 2010 2009 2008

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (23 results)

  • [Journal Article] The impact of abdominal shape index of patients on laparoscopy-assisted distal gastrectomy for early gastric cancer. Langenbecks Arch Surg2011

    • Author(s)
      Ojima T, Iwahashi M, Nakamori M, Nakamura M, Takifuji K, Katsuda M, Iida T, Tsuji T, Hayata K, Yamaue H
    • Journal Title

      Epub ahead of print

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of different classes of CpG-ODN in augmenting the generation of human epitope peptide-specific CTLs2011

    • Author(s)
      Katsuda M, Iwahashi M, Matsuda K, Miyazawa M, Nakamori M, Nakamura M, Ojima T, Iida T, Hayata K, Yamaue H
    • Journal Title

      Int J Oncol

      Volume: 39(5) Pages: 1295-302

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Optimal Period for the Prophylactic Administration of Neutrophil Elastase Inhibitor for Patients with Esophageal Cancer Undergoing Esophagectomy2011

    • Author(s)
      Iwahashi M, Nakamori M, Nakamura M, Ojima T, Naka T, Yamaue H
    • Journal Title

      World J Surg

      Volume: 35(7) Pages: 1573-9

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cells adenovirally-transduced with full-length mesothelin cDNA elicit mesothelin-specific cytotoxicity against pancreatic cancer cell lines in vitro2011

    • Author(s)
      Miyazawa M, Iwahashi M, Ojima T, Katsuda M, Nakamura M, Nakamori M, Ueda K, Naka T, Hayata K, Iida T, Yamaue H
    • Journal Title

      Cancer Lett

      Volume: 305(1) Pages: 32-9

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-infiltrating CD4+Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer2011

    • Author(s)
      Iida T, Iwahashi M, Katsuda M, Ishida K, Nakamori M, Nakamura M, Naka T, Ojima T, Ueda K, Hayata K, Nakamura Y, Yamaue H
    • Journal Title

      Oncol Rep

      Volume: 25(5) Pages: 1271-7

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+T cell response in patients with metastatic esophageal squamous cell carcinoma2010

    • Author(s)
      Iwahashi M, Katsuda M, Nakamori M, Nakamura M, Naka T, Ojima T, Iida T, Yamaue H
    • Journal Title

      Cancer Sci

      Volume: 101(12) Pages: 2510-7

    • NAID

      10027834170

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological characteristics of remnant gastric cancer after a distal gastrectomy2010

    • Author(s)
      Ojima T, Iwahashi M, Nakamori M, Nakamura M, Naka T, Katsuda M, Iida T, Tsuji T, Hayata K, Takifuji K, Yamaue H
    • Journal Title

      J Gastrointest Surg

      Volume: 14(2) Pages: 277-81

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bacillus Calmette-Guerin cell-wall skeleton enhances the killing activity of cytotoxic lymphocyte-activated human dendritic cells transduced with the prostate-specific antigen gene2009

    • Author(s)
      Fujii R, Iwahashi M, Kikkawa K, Inagaki T, Kohjimoto Y, Ojima T, Mori T, Kuramoto T, Nishizawa S, Azuma I, Yamaue H, Shinka T, Hara I
    • Journal Title

      BJU Int

      Volume: 104(11) Pages: 1766-73

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Optimal dose of preoperative enteral immunonutrition for patients with esophageal cancer2009

    • Author(s)
      Nakamura M, Iwahashi M, Takifuji K, Nakamori M, Naka T, Ishida K, Ojima T, Iida T, Katsuda M, Hayata K, Yamaue H
    • Journal Title

      Surg Today

      Volume: 39(10) Pages: 855-60

    • NAID

      10025555140

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of allogeneic blood transfusions and long-term survival of patients with gastric cancer after curative gastrectomy2009

    • Author(s)
      Ojima T, Iwahashi M, Nakamori M, Nakamura M, Naka T, Katsuda M, Iida T, Hayata K, Yamaue H
    • Journal Title

      J Gastrointest Surg

      Volume: 13(10) Pages: 1821-30

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of double tract reconstruction after total gastrectomy in patients with gastric cancer : prospective randomized controlled trial2009

    • Author(s)
      Iwahashi M, Nakamori M, Nakamura M, Naka T, Ojima T, Iida T, Katsuda M, Ueda K, Yamaue H
    • Journal Title

      World J Surg

      Volume: 33(9) Pages: 1882-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of the prognostic factors and evaluation of surgical treatment for synchronous liver metastases from gastric cancer2009

    • Author(s)
      Ueda K, Iwahashi M, Nakamori M, Nakamura M, Naka T, Ishida K, Ojima T, Yamaue H
    • Journal Title

      Langenbecks Arch Surg

      Volume: 394(4) Pages: 647-53

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Influence of overweight on patients with gastric cancer after undergoing curative gastrectomy : an analysis of 689 consecutive cases managed by a single center2009

    • Author(s)
      Ojima T, Iwahashi M, Nakamori M, Nakamura M, Naka T, Ishida K, Ueda K, Katsuda M, Iida T, Tsuji T, Yamaue H
    • Journal Title

      Arch Surg

      Volume: 144(4) Pages: 351-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 腫瘍抗原遺伝子導入樹状細胞を用いた癌ワクチン療法2010

    • Author(s)
      尾島敏康, 岩橋誠, 中村公紀, 宮澤基樹, 中森幹人, 勝田将裕, 飯田武, 早田啓治, 辻俊明, 山上裕機
    • Organizer
      第23回日本バイオセラピー学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] Vaccination using dendritic cells transduced with ubiquitin-mesothelin fusion gene for pancreatic cancer2010

    • Author(s)
      Motoki Miyazawa
    • Organizer
      第69回 日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 膵癌に対するMesothelinを標的とした樹状細胞ワクチン療法の基礎的検討2010

    • Author(s)
      宮澤基樹
    • Organizer
      第31回癌免疫外科研究会
    • Place of Presentation
      大阪
    • Year and Date
      2010-05-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] 胃癌腫瘍微小環境におけるTregおよびTh17の動態解析2010

    • Author(s)
      飯田武, 岩橋誠, 勝田将裕, 中森幹人, 中村公紀, 石田興一郎, 中禎二, 尾島敏康, 早田啓治, 辻俊明, 山上裕機
    • Organizer
      第110回日本外科学会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-04-09
    • Related Report
      2010 Final Research Report
  • [Presentation] Mesothelin遺伝子導入樹状細胞を用いた膵癌に対する特異的CTLの誘導2010

    • Author(s)
      宮澤基樹, 岩橋誠, 尾島敏康, 勝田将裕, 中禎二, 中村公紀, 山上裕機
    • Organizer
      第110回日本外科学会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-04-09
    • Related Report
      2010 Final Research Report
  • [Presentation] 癌治療を実践する外科医が行う基礎研究の意義2010

    • Author(s)
      岩橋誠, 中森幹人, 中村公紀, 中禎二, 尾島敏康, 上田健太郎, 勝田将裕, 松田健司, 山上裕機
    • Organizer
      第110回日本外科学会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-04-09
    • Related Report
      2010 Final Research Report
  • [Presentation] Mesothelin遺伝子導入樹状細胞を用いた膵癌に対する特異的CTLの誘導2010

    • Author(s)
      宮澤基樹
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-04-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Mesothelin遺伝子導入樹状細胞を用いた膵癌免疫療法2009

    • Author(s)
      宮澤基樹, 岩橋誠, 尾島敏康, 勝田将裕, 中村公紀, 中禎二, 中森幹人, 山上裕機
    • Organizer
      第22回日本バイオセラピー学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 胃癌腫瘍微小環境におけるTh17およびTregの動態からみた癌免疫逃避機構の解析2009

    • Author(s)
      飯田武, 岩橋誠, 勝田将裕, 中森幹人, 中村公紀, 石田興一郎, 中禎二, 尾島敏康, 早田啓治, 辻俊明, 山上裕機
    • Organizer
      第22回日本バイオセラピー学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] CpG-ODNによる癌抗原特異的エフェクター細胞の効率的誘導と抗腫瘍活性増強効果2009

    • Author(s)
      勝田将裕, 岩橋誠, 中森幹人, 中村公紀, 松田健司, 中禎二, 尾島敏康, 飯田武, 宮澤基樹, 角田卓也, 中村祐輔, 山上裕機
    • Organizer
      第22回日本バイオセラピー学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 進行食道癌に対するCpG-B併用新規腫瘍抗原ペプチドワクチン療法:第I相臨床試験の結果からみた将来展望2009

    • Author(s)
      岩橋誠, 勝田将裕, 中森幹人, 中村公紀, 飯田武, 中禎二, 尾島敏康, 松田健司, 角田卓也, 中村祐輔, 山上裕機
    • Organizer
      第22回日本バイオセラピー学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Tumor-infiltrating CD4+T cells secreting IL-17 Th17 promotes tumor growth in human gastric cancer2009

    • Author(s)
      飯田武, 岩橋誠, 勝田将裕, 石田興一郎, 中森幹人, 中村公紀, 中禎二, 尾島敏康, 山上裕機
    • Organizer
      第68回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Immunotherapy using genetically modified DCs co-expressing CEA and GM-CSF2009

    • Author(s)
      尾島敏康
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] CpG-ODNs augment cytotoxic activity of peptide-specific CTLs from patients with esophageal cancer2009

    • Author(s)
      勝田将裕, 岩橋誠, 中森幹人, 中村公紀, 松田健司, 中禎二, 尾島敏康, 飯田武, 宮澤基樹, 山上裕機
    • Organizer
      第68回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Immunotherapy using genetically modified DCs co-expressing CEA and GM-CSF2009

    • Author(s)
      尾島敏康, 岩橋誠, 中村公紀, 中森幹人, 中禎二, 勝田将裕, 飯田武, 早田啓治, 上田健太郎, 山上裕機
    • Organizer
      第68回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Phase I trial of vaccination of tumor specific peptides combined with CpG-B for patients with esophageal cancer2009

    • Author(s)
      岩橋誠, 勝田将裕, 中森幹人, 中村公紀, 宮澤基樹, 松田健司, 中禎二, 尾島敏康, 飯田武, 角田卓也, 中村祐輔, 山上裕機
    • Organizer
      第68回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-01
    • Related Report
      2010 Final Research Report
  • [Presentation] 消化器癌ワクチンの臨床応用進行食道癌に対するCpG-B併用URLC10およびTTKエピトープペプチドワクチン療法の第I相臨床試験2009

    • Author(s)
      勝田将裕, 岩橋誠, 松田健司, 宮澤基樹, 中森幹人, 中村公紀, 中禎二, 尾島敏康, 飯田武, 山上裕機
    • Organizer
      第64回日本消化器外科学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-17
    • Related Report
      2010 Final Research Report
  • [Presentation] Mesothelin遺伝子導入樹状細胞を用いた膵癌免疫療法2008

    • Author(s)
      宮澤基樹, 岩橋誠, 尾島敏康, 勝田将裕, 飯田武, 中禎二, 中森幹人, 中村公紀, 松田健司, 山上裕機
    • Organizer
      第21回日本バイオセラピー学会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-18
    • Related Report
      2010 Final Research Report
  • [Presentation] 腫瘍抗原遺伝子導入樹状細胞を用いた癌ワクチン療法(臨床応用に向けて)2008

    • Author(s)
      尾島敏康, 岩橋誠, 中村公紀, 中森幹人, 宮澤基樹, 中禎二, 上田健太郎, 勝田将裕, 飯田武, 山上裕機
    • Organizer
      第21回日本バイオセラピー学会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-18
    • Related Report
      2010 Final Research Report
  • [Presentation] 癌ワクチン療法後の再燃腫瘍に対する腫瘍RNA導入樹状細胞を用いた治療戦略の検討2008

    • Author(s)
      中禎二, 岩橋誠, 中村公紀, 尾島敏康, 勝田将裕, 松田健司, 中森幹人, 宮澤基樹, 石田興一郎, 山上裕機
    • Organizer
      第21回日本バイオセラピー学会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-18
    • Related Report
      2010 Final Research Report
  • [Presentation] 癌ワクチン療法後の再燃腫瘍に対する腫瘍RNA導入樹状細胞を用いた治療戦略の検討2008

    • Author(s)
      中 禎二
    • Organizer
      第21回日本バイオセラピィ学会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] CEA遺伝子Th 1-type oytokine遺伝子導入樹状細胞を用いた癌ワクチン療法-CEA transgenic miceを用いた検討-2008

    • Author(s)
      尾島敏康
    • Organizer
      第46回 日本癌治療学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-31
    • Related Report
      2008 Annual Research Report
  • [Presentation] CEA遺伝子Th 1-type cytokine遺伝子導入樹状細胞を用いた癌ワクチン療法-CEA transgenic miceを用いた検討-2008

    • Author(s)
      尾島敏康, 岩橋誠, 中村公紀, 中森幹人, 中禎二, 上田健太郎, 石田興一郎, 勝田将裕, 飯田武, 宮澤基樹, 山上裕機
    • Organizer
      第46回日本癌治療学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-30
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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