Development of peptide vaccination targeting novel musculoskeletal sarcoma antigens

2011 Fiscal Year Final Research Report

• Project/Area Number: 20390403
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Sapporo Medical University
• Principal Investigator: WADA Takuro 札幌医科大学, 道民医療推進学講座, 特任教授 (00244369)
• Co-Investigator(Kenkyū-buntansha): YMASHITA Toshihiko 札幌医科大学, 医学部, 教授 (70244366) ; SATO Noriyuki 札幌医科大学, 医学部, 教授 (50158937)
• Project Period (FY): 2008 – 2011
• Keywords: 分子標的治療 / 骨軟部肉腫 / 癌ワクチン / ペプチド

Research Abstract

We performed phase I clinical peptide vaccination trials for patients with disseminated synovial sarcoma or osteosarcoma. For synovial sarcoma, the trial was completed and the safety and efficacy of SYT-SSX peptide vaccination was confirmed. For osteosarcoma, the trial is continued.
We identified cancer-stem like cells from malignant fibrous histiocytoma of the bone and epithelial sarcoma. Furthermore, we established autologous cytotoxic T-lymphocyte clone recognizing cancer-stem like cells in the context of HLA class I. These observations open the door toward immunotherapy targeting cancer-stem like cells.

Research Products

• [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 Pages: 380-385
  • Peer Reviewed
• [Journal Article] Autologous CTL response against cancer stem-like cells/cacer-initiating cells of bone malignant fibrous histiocytoma (2011)
  • Author(s): Kano M, Tsukahara T, Emori M, Masaki Murase, Torigoe T, Kawaguchi S, Wada T, Yamashita T, Sato N
  • Journal Title: Cancer Sci Volume: 102 Pages: 1443-1447
  • Peer Reviewed
• [Journal Article] Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas (2009)
  • Author(s): Murase M, Kano M, Tsukahara T, Takahashi A, Torigoe T, Kawaguchi S, Kimura S, Wada T, Uchihashi Y, Kondo T, Yamashita T, Sato N
  • Journal Title: Br J Cancer Volume: 101 Pages: 1425-1432
  • Peer Reviewed
• [Journal Article] Scythe/BAT3 regulates apoptotic cell death induced by papillomavirus binding factor in human osteosarcoma (2009)
  • Author(s): Tsukahara T, Kimura S, Ichimiya S, Torigoe T, Kawaguchi S, Wada T, Yamashita T, Sato N
  • Journal Title: Cancer Sci Volume: 100 Pages: 47-53
  • Peer Reviewed
• [Journal Article] HLA-A 0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor. (2009)
  • Author(s): Tsukahara T, Kawaguchi S, Torigoe T, Murase M, Wada T, Kaya M, Nagoya S, Yamashita T, Sato N
  • Journal Title: J Transl Med
  • Peer Reviewed
• [Journal Article] Overexpression of papillomavirus binding factor in Ewing's sarcoma family of tumors conferring poor prognosis (2008)
  • Author(s): Yabe H, Tsukahara T, Kawaguchi S, Wada T, Sato N, Morioka H, Yabe H
  • Journal Title: Oncol Rep Volume: 19 Pages: 129-134
  • Peer Reviewed
• [Journal Article] Clonal T-cell response against autologous pleomorphic malignant fibrous histiocytoma antigen presented by retrieved HLA-A (2008)
  • Author(s): Kimura S, Kozakai Y, Kawaguchi S, Tsukahara T, Ida K, Murase M, Matsumura T, Kaya M, Torigoe T, Wada T, Sato N, Yamashita T
  • Journal Title: J Orthop Res Volume: 26 Pages: 271-278
  • Peer Reviewed
• [Journal Article] Antigenic peptide vaccination : Provoking immune response and clinical benefit for cancer (2008)
  • Author(s): Tsukahara T, Torigoe T, Tamura Y, Wada T, Kawaguchi S, Tsuruma T, Hirata K, Yamashita T, Sato N
  • Journal Title: Curr Immunol Rev Pages: 235-241
  • Peer Reviewed
• [Journal Article] Prognostic impact and immunogenicity of a novel osteosarcoma antigen, papillomavirus binding factor, in patients with osteosarcoma. (2008)
  • Author(s): Tsukahara T, Kawaguchi S, Torigoe T, Kimura S, Murase M, Ichimiya S, Wada T, Kaya M, Nagoya S, Ishii T, Tatezaki S, Yamashita T, Sato N
  • Journal Title: Cancer Sci Volume: 99 Pages: 368-375
  • Peer Reviewed
• [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: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20111003-05
• [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: 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: 20110714-15
• [Presentation] Scythe/BAT3 regulates apoptotic cell death induced (2010)
  • Author(s): Tomohide Tsukahara, Shigeharu Kimura, Shingo Ichimiya, Satoshi Kawaguchi, Masanobu Kano, Takuro Wada, Toshihiko Torigoe, Toshihiko Yamashita, Noriyuki Sato
  • Organizer: The osteosarcoma antigen PBF in human osteosarcoma 16th Annual Connective Tissue Oncology Society Meeting
  • Place of Presentation: Paris
  • Year and Date: 2010-11-13
• [Presentation] HLA-A2拘束性骨肉腫抗原PBFペプチドに対する基礎的研究と第1相臨床試験 (2009)
  • Author(s): 塚原智英, 川口哲, 和田卓郎, 名越智, 加谷光規, 嘉野真允, 山下敏彦, 鳥越俊彦, 佐藤昇志
  • Organizer: 第24回日本整形外科学会基礎学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20091105-06
• [Presentation] Scythe/BAT3はPBFに誘導されるAIF依存的な骨肉腫の細胞死を制御する (2009)
  • Author(s): 塚原智英, 木村重治, 川口哲, 嘉野真允, 和田卓郎, 山下敏彦, 一宮慎吾, 鳥越俊彦, 佐藤昇志
  • Organizer: 第42回日本整形外科学会骨軟部腫瘍学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20090716-17
• [Presentation] Characterization and clinical vaccination study of HLA-A* 0201-restricted epitope of the osteosarcoma antigen PBF (2009)
  • Author(s): 塚原智英, 川口哲, 嘉野真允, 和田卓郎, 山下敏彦, 鳥越俊彦, 高橋あかり, 佐藤昇志
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20090624-25
• [Presentation] The third vaccination trial of SYT-SSX junction peptide in patients with disseminated synovial sarcoma (2008)
  • Author(s): Wada T, Kawaguchi S, Tsukahara T, Ida K, Murase M, Nagoya S, Kaya M, Torigoe T, Sato N, Yamashita T
  • Organizer: 14th Annual CTOS Meeting
  • Place of Presentation: London
  • Year and Date: 20081113-15
• [Presentation] Scythe/BAT3 regulates apoptotic cell death induced by papillomavirus binding factor in human osteosarcoma (2008)
  • Author(s): 塚原智英, 木村重治, 川口哲, 和田卓郎, 山下敏彦, 一宮慎吾, 鳥越俊彦, 佐藤昇志
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20081028-30
• [Presentation] 新規骨肉腫抗原PBF由来ペプチドに対するHLA-A2陽性骨肉腫患者の免疫応答 (2008)
  • Author(s): 塚原智英, 川口哲, 村瀬正樹, 和田卓郎, 名越智, 加谷光規, 山下敏彦, 鳥越俊彦, 佐藤昇志
  • Organizer: 第41回日本整形外科学会骨軟部腫瘍学術集会
  • Place of Presentation: 浜松市
  • Year and Date: 20080717-18
• [Book] 骨軟骨腫,内軟骨腫,単純性骨嚢腫-今日の治療指針2011年版. (2011)
  • Author(s): 和田卓郎
  • Total Pages: 984
  • Publisher: 医学書院
• [Book] 傍骨性骨肉腫-アトラス骨・関節画像診断骨軟部腫瘍 (2010)
  • Author(s): 加谷光規, 和田卓郎
  • Total Pages: 14-5
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://web.sapmed.ac.jp/orsurg/index.html
• [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
  • Industrial Property Number: 209822007. 2-2403PCT/JP2009068013
  • Acquisition Date: 2011-06-29
  • Overseas
• [Patent(Industrial Property Rights)] 腫瘍抗原ペプチド及びその利用 (2008)
  • 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
  • Industrial Property Number: 特願、2008-270078
  • Acquisition Date: 2008-10-20