Immunological response against bone and soft tissue sarcoma

• Project/Area Number: 22689041
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Sapporo 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: ¥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.

Research Products

• [Journal Article] ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Prognostic significance of HLA class I expression in Ewing's sarcoma family of tumors (2011)
  • 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
  • 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 patients (2011)
  • 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
  • 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
• [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
• [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
• [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
• [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
• [Presentation] Generation of TCR-like antibody against HLA/peptide complex of an osteosarcoma antigen PBF (2011)
  • 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
• [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
• [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
• [Presentation] Generation of TCR-like antibody against HLA/peptide complex of an osteosarcoma antigen PBF (2011)
  • 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
• [Presentation] Scythe/BAT3 regulates apoptotic cell death induced by the osteosarcoma antigen PBF in human osteosarcoma (2010)
  • 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
• [Presentation] Development of peptide vaccination therapy targeting apoptosis regulator protein PBF for patients with osteosarcoma (2010)
  • 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
• [Presentation] Development of peptide vaccination therapy targeting apoptosis regulator protein PBF for patients with osteosarcoma (2010)
  • Author(s): Tomohide Tsukahara
  • Organizer: 16^<th> International Congress of Immunology
  • Place of Presentation: Kobe
• [Patent(Industrial Property Rights)] Tumor antigen peptide and use thereof (2011)
  • 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
  • Overseas