Developing T-cell based immunotherapy using ubiquitously expressing tumor-associated antigen, Aurora-A kinase and FAK

• Project/Area Number: 21590424
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Asahikawa Medical College
• Principal Investigator: KOBAYASHI Hiroya 旭川医科大学, 医学部, 教授 (90280867)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: CD4 ヘルパーT 細胞 / 腫瘍抗原 / ペプチド / HLA / Aurora-A / FAK / ヘルパーT細胞 / 癌抗原 / 腫瘍免疫 / CD4ヘルパーT細胞 / 免疫治療 / ワクチン

Research Abstract

Focal adhesion kinase (FAK) and Aurora kinase A (Aurora-A) are ubiquitously expressed kinase involved in cancer progression and with poor prognosis that are found overexpressed in various types of cancer. To validate FAK and Aurora-A as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and cancer patients. Synthetic peptides correspond to potential HTL epitopes induced HTL responses that directly recognized FAK/Aurora-A-expressing tumor cells and autologous dendritic cells pulsed with these TAA-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK/Aurora-A peptides were recognized by cancer patient's CD4 T cells, the T helper peptide epitopes might be used for designing T cell-based immunotherapy for FAK/Aurora-A-expressing cancers.

Research Products

• [Journal Article] Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 asimmunotherapeutic targets for lung cancer (2011)
  • Author(s): Hayashi S, Kumai T, Matsuda Y, Aoki N, SatoK, Kimura S, Kitada M, Tateno M, Celis E, Kobayashi H.
  • Journal Title: J Transl Med Volume: 9 Issue: 1 Pages: 191-191
  • DOI: 10.1186/1479-5876-9-191
• [Journal Article] Characterization of human CD4 helper T cellresponses against Aurora kinase A (2010)
  • Author(s): Kobayashi H, Azumi M, Hayashi S, Sato K, Aoki N, Kimura S, Kakizaki H, NagatoT, Harabuchi Y, Tateno M, Celis E
  • Journal Title: CancerImmunol Immunother Volume: 59(7) Issue: 7 Pages: 1029-39
  • DOI: 10.1007/s00262-010-0826-0
• [Journal Article] Characterization of human CD4 helper T cell responses against Aurora-A kinase A (2010)
  • Author(s): Hiroya Kobayashi
  • Journal Title: Cancer Immunol Immunother Volume: 59 Pages: 1029-1039
  • Peer Reviewed
• [Journal Article] Six-Transmembrane epithelial antigen of the prostate as an immunother-apeutic target for renal cell and bladder cancer (2010)
  • Author(s): Makoto Azumi
  • Journal Title: J Urol Volume: 183 Pages: 2036-2044
  • Peer Reviewed
• [Journal Article] Focal adhesion kinase as animmunother apeutic target. (2009)
  • Author(s): Kobayashi H, Azumi M, Kimura Y, Sato K, Aoki N, Kimura S, Honma M, Iizuka H, Tateno M, Celis E.
  • Journal Title: Cancer Immunol Immunother Volume: 58(6) Issue: 6 Pages: 931-40
  • DOI: 10.1007/s00262-008-0608-0
• [Journal Article] Focal adhesion kinase as an immunotherapeutic target (2009)
  • Author(s): Hiroya Kobayashi
  • Journal Title: Cancer Immunology Immunotherapy 58 Pages: 931-940
  • Peer Reviewed
• [Presentation] Tヘルパー応答から考察した癌抗原タンパク質としてのAurora-A kinaseの有用性 (2010)
  • Author(s): 小林博也
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京都
  • Year and Date: 2010-04-29
• [Presentation] 癌免疫、アレルギー制御に関わるHLAクラスII分子結合性ペプチド抗原の分子病理学的解析 (2010)
  • Author(s): 小林博也(代表者)
  • Organizer: 第56回日本病理学会秋期特別総会
  • Place of Presentation: 北九州市
• [Presentation] Tヘルパー応答から考察した癌抗原タンパク質してのAurora-A kinaseの有用性 (2010)
  • Author(s): 小林博也(代表者)
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 横浜市
• [Presentation] Tヘルパー応答から考察した免疫標的分子としてのFAKの可能性 (2009)
  • Author(s): 小林博也
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] 免疫標的分子としてのFocal adhesion kinase(FAK)の可能性 (2009)
  • Author(s): 小林博也
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-05-01
• [Presentation] Tヘルパー応答から考察した免疫標的分子としてのFAKの可能性 (2009)
  • Author(s): 小林博也(代表者)
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜市
• [Presentation] 免疫標的分子としてのFocal adhesion kinase(FAK)の可能性 (2009)
  • Author(s): 小林博也(代表者)
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都市