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Immunological response against bone and soft tissue sarcoma

Research Project

Project/Area Number 22689041
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionSapporo Medical University

Principal Investigator

TSUKAHARA Tomohide  札幌医科大学, 医学部, 助教 (20404634)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
Fiscal Year 2011: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2010: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Keywords骨 / 軟部腫瘍学 / 骨肉腫抗原 / HLA/ペプチド複合体 / ファージディスプレイライブラリ
Research Abstract

We performed phase I clinical peptide vaccination trial for patient with osteosarcoma. We used HLA-A24 or HLA-A2-restricted PBF-derived peptides as the vaccines with incomplete Freund' adjuvant. The peptide-specific CTL responses were observed in two HLA-A24+ and one HLA-A2+patients. After the confirmation of safety and immunogenicity of the peptide vaccines, we will plan phase II trial as adjuvant therapy after operative resection combined with post-operative chemotherapy.
In addition, we generated artificial antibody against HLA/peptide complex recognized by CTL(natural epitope antibody). scFv phage display library was constructed from RNA derived from human naive PBMC and tonsiles, followed by biopanning using HLA-A2/PBF peptide complex. After panning, one scFv clone was obtained and converted into hIgG1 subtype(scFv-hIgG1). The scFv-hIgG1 recognized peptide-pulsed T2 cells by FACS and showed high affinity by SPR analysis. This natural epitope antibody might be useful for the detection of HLA/peptide complex on tumor cells and for the development of genetically engineered CTLs expressing natural epitope antibody for adoptive cell therapy.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (17 results)

All 2012 2011 2010

All Journal Article (6 results) (of which Peer Reviewed: 4 results) Presentation (10 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells2012

    • Author(s)
      Matsuzaki J,Torigoe T,Hirohashi Y, Kamiguchi K,Tamura Y, Tsukahara T,Kubo T, Takahashi A, Nakazawa E,Saka E, Yasuda K,Takahashi S,Sato N.
    • Journal Title

      Carcinogenesis

      Volume: 33 Issue: 5 Pages: 996-1003

    • DOI

      10.1093/carcin/bgs118

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma2011

    • Author(s)
      Kano, M., Tsukahara, T., Emori, M., Murase, M., Torigoe, T., Kawaguchi, S., Wada, T., Yamashita, T., Sato, N.
    • Journal Title

      Cancer Sci

      Volume: 102 Issue: 8 Pages: 1443-1137

    • DOI

      10.1111/j.1349-7006.2011.01962.x

    • NAID

      10030241866

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of HLA class I expression in Ewing's sarcoma family of tumors2011

    • Author(s)
      Yabe H, Tsukahara T, Kawaguchi S, Wada T, Torigoe T, Sato N, Terai C, Aoki M, Hirose S, Morioka H, Yabe H
    • Journal Title

      J Surg Oncol

      Volume: 103 Issue: 5 Pages: 380-385

    • DOI

      10.1002/jso.21829

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients2011

    • Author(s)
      Kameshima, H., Tsuruma, T., Torigoe, T., Takahashi, A., Hirohashi, Y., Tamura, Y., Tsukahara, T., Ichimiya, S., Kanaseki, T., Iwayama, Y., Sato, N., Hirata, K.
    • Journal Title

      Cancer Sci

      Volume: 102 Issue: 6 Pages: 1181-1187

    • DOI

      10.1111/j.1349-7006.2011.01918.x

    • NAID

      10029294487

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 骨軟部肉腫に対するペプチドワクチン療法2011

    • Author(s)
      江森誠人, 塚原智英, 川口哲, 和田卓郎
    • Journal Title

      日本臨床

      Volume: 9 Pages: 1670-1673

    • Related Report
      2011 Final Research Report
  • [Journal Article] 骨・軟部肉腫に対するペプチドワクチン療法2011

    • Author(s)
      江森誠人, ほか
    • Journal Title

      日本臨床

      Volume: 69 Pages: 1670-1673

    • Related Report
      2011 Annual Research Report
  • [Presentation] Generation of TCE-like antibody against HLA/peptide complex of an osteosarcoma antigen PBF「ワークショップ48:がん免疫療法」2011

    • Author(s)
      塚原智英, ほか
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      幕張
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨軟部肉腫における癌幹細胞を標的とする免疫療法「パネルディスカッションI幹細胞研究の骨・軟部腫瘍学への応用」2011

    • Author(s)
      塚原智英, ほか
    • Organizer
      第44回日本整形外科学会骨軟部腫瘍学術集会
    • Place of Presentation
      京都
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Generation of TCR-like antibody against HLA/peptide complex of an osteosarcoma antigen PBF「ワークショップ48 :がん免疫療法」2011

    • Author(s)
      塚原智英, 鳥越俊彦, 佐藤昇志, 和田卓郎
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report
  • [Presentation] Generation of TCR-like antibody against HLA/peptide complex of an osteosarcoma antigen PBF2011

    • Author(s)
      塚原智英, 鳥越俊彦, 佐藤昇志, 和田卓郎
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨肉腫抗原を標的としたTCR類似抗体の開発「MWSワークショップ」2011

    • Author(s)
      塚原智英, 鳥越俊彦, 佐藤昇志, 和田卓郎
    • Organizer
      日本臨床免疫学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨軟部肉腫における癌幹細胞を標的とする免疫療法「パネルディスカッションI幹細胞研究の骨・軟部腫瘍学への応用」2011

    • Author(s)
      塚原智英, 佐藤昇志, 嘉野真允, 江森誠, 山下敏彦, 和田卓郎
    • Organizer
      日本整形外科学会骨軟部腫瘍学術集会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Generation of TCR-like antibody against HLA/peptide complex of an osteosarcoma antigen PBF2011

    • Author(s)
      塚原智英, 鳥越俊彦, 佐藤昇志, 和田卓郎
    • Organizer
      日本がん免疫学会総会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report
  • [Presentation] Scythe/BAT3 regulates apoptotic cell death induced by the osteosarcoma antigen PBF in human osteosarcoma2010

    • Author(s)
      Tomohide Tsukahara, Shigeharu Kimura, Shingo Ichimiya, Satoshi Kawaguchi, Masanobu Kano, Takuro Wada, Toshihiko Torigoe, Toshihiko Yamashita, Noriyuki Sato
    • Organizer
      14th Annual Connective Tissue Oncology Society Meeting
    • Place of Presentation
      Paris, France
    • Related Report
      2011 Final Research Report
  • [Presentation] Development of peptide vaccination therapy targeting apoptosis regulator protein PBF for patients with osteosarcoma2010

    • Author(s)
      Tomohide Tsukahara, Satoshi Kawaguchi, Toshihiko Torigoe, Shingo Ichimiya, Masanobu Kano, Akari Takahashi, Satoshi Nagoya, Takuro Wada, Toshihiko Yamashita, Noriyuki Sato
    • Organizer
      Immunology : 2010
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] Development of peptide vaccination therapy targeting apoptosis regulator protein PBF for patients with osteosarcoma2010

    • Author(s)
      Tomohide Tsukahara
    • Organizer
      16^<th> International Congress of Immunology
    • Place of Presentation
      Kobe
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] Tumor antigen peptide and use thereof2011

    • Inventor(s)
      佐藤昇志,塚原智英,川口哲,和田卓郎
    • Industrial Property Rights Holder
      佐藤昇志,塚原智英,川口哲,和田卓郎
    • Acquisition Date
      2011-06-29
    • Related Report
      2011 Final Research Report
    • Overseas

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Published: 2010-08-23   Modified: 2016-04-21  

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