Targeting T cell negative pathway as a novel anticancer therapy

• Project/Area Number: 19591491
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Nara Medical University
• Principal Investigator: MASAYUKI Sho Nara Medical University, 講師 (50364063)
• Co-Investigator(Kenkyū-buntansha): 赤堀 宇広 , 医学部・付属病院, 研究員 (10423922)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 外科総論 / 消化器癌 / 抗体療法 / PD-1 / CTLA-4 / T細胞

Research Abstract

in vivoマウス腫瘍実験系において, T細胞Negative PathwayであるPD-1やCTLA-4の阻害により, 有意な抗腫瘍効果を見いだした. 特にPD-1/CTLA-4経路同時阻害により, 極めて強力な抗腫瘍効果を誘導する事を確認した. さらに組織学的検討にて肝臓, 小腸等に明らかな自己免疫様の異常はみられず, マウスに体重減少等もみられなかったことから, 治療の安全性も確認された. さらにB7-H3抗体による治療を行ったところ, 有意な抗腫瘍効果を認めた. またPD-1阻害, B7-H3阻害と化学療法との併用効果について検討し, 相乗効果を認め, 今後の臨床応用の可能性示唆された.

Research Products

• [Journal Article] 癌転移機構におけるT細胞Negative Pathwayの関与と新たな治療戦略 (2008)
  • Author(s): 庄雅之, 野見武男, 赤堀宇広, 中村信治, 山戸一郎, 中島祥介
  • Journal Title: 癌の臨床 54(3) Pages: 175-180
  • NAID: 110006330424
• [Journal Article] 消化器癌におけるT細胞negative pathwayの意義と新たな治療戦略 (2008)
  • Author(s): 庄雅之, 野見武男, 赤堀宇広, 中村信治, 山戸一郎, 中島祥介
  • Journal Title: Biotherapy 22(2) Pages: 105-110
• [Journal Article] 癌転移機構におけるT細胞Negative Pathwayの関与と新たな治療戦略 (2008)
  • Author(s): 庄 雅之
  • Journal Title: 癌の臨床 54 Pages: 175-180
• [Journal Article] 消化器癌におけるT細胞negative pathwayの意義と新たな治療戦略 (2008)
  • Author(s): 庄 雅之
  • Journal Title: Biotherapy 22 Pages: 105-110
• [Journal Article] Significance and Therapeutic Potential of Programmed Death-1 Ligand/Programmed Death-1 Pathway in Human Pancreatic Cancer. 2007 (2007)
  • Author(s): Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H, Nakamura S, Enomoto K, Yagita H, Azuma M, Nakajima Y. Clinical
  • Journal Title: Clin Cancer Res 3(7) Pages: 2151-7
• [Journal Article] Clinical Significance and Therapeutic Potential of the Programmed Death-1 Ligand/Programmed Death-1 Pathway in Human Pancreatic Cancer (2007)
  • Author(s): Takeo Nomi, Masayuki Sho, et. al.
  • Journal Title: Clin Cancer Res 13 Pages: 2151-2157
  • Peer Reviewed
• [Presentation] New insights into targeting T cell negative pathway in tumor immunity (2008)
  • Author(s): Masayuki Sho, Takeo Nomi, Takahiro Akahori, Ichiro Yamato, Hiromichi Kanehiro, Miyuki Azuma, Hisaya Akiba, Hideo Yagita, Yoshiyuki Nakajima
  • Organizer: AACR 2008 annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-04-15
• [Presentation] Significance of T cell negative regulatory pathway in human gastrointestinal cancer (2007)
  • Author(s): Sho M, et. al.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] 難治性消化器癌におけるT細胞Negative Signalの臨床的意義とその制御による新規癌治療戦略 (2007)
  • Author(s): 庄 雅之, 他
  • Organizer: 第62回日本消化器外科学会定期学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-18
• [Presentation] Targeting T cell negative pathway induces powerful and long-lasting antitumor effect in vivo (2007)
  • Author(s): Masayuki Sho, Takeo Nomi, Takahiro Akahori, Hiromichi Kanehiro, Miyuki Azuma, Hideo Yagita, Yoshiyuki Nakajima
  • Organizer: AACR 2007 annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-04-15
• [Presentation] Targeting T cell negative pathway induces powerful and long-lasting antitumor effect in vivo (2007)
  • Author(s): Sho M, et. al.
  • Organizer: 2007 AACR annual meeting
  • Place of Presentation: Los Angels,CA,USA
  • Year and Date: 2007-04-15
• [Presentation] Significance of T cell negative regulatory pathway in human gastrointestinal cancer (2007)
  • Author(s): Masayuki Sho, Takeo Nomi, Takahiro Akahori, Hiromichi Kanehiro, Miyuki Azuma, Hideo Yagita, Yoshiyuki Nakajima
  • Organizer: 第66回日本癌学会学術集会
  • Place of Presentation: 横浜