Development of immnotherapy for gynecological cancer and microenvironment

• Project/Area Number: 24592512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: SHIBATA Kiyosumi 名古屋大学, 医学(系)研究科(研究院), 准教授 (90335026)
• Co-Investigator(Kenkyū-buntansha): KAJIYAMA Hiroaki 名古屋大学, 大学院医学系研究科, 准教授 (00345886)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌免疫療法 / 癌微小環境 / 腹膜播種 / 免疫抑制 / 臨床試験 / 癌抗原 / 難治性卵巣癌 / ペプチドワクチン療法 / サイトカイン / ペプチドワクチン

Outline of Final Research Achievements

We performed a phase II clinical trial of HLA-A24 and A2 restrictive Glypican-3 (GPC3) peptide vaccine for 92 ovarian clear cell carcinoma patients as one of the immunotherapy for refractory ovarian carcinoma. We confirmed three partial responses in a advanced patient. However our resuths showed that the patients with peritoneal dissemination had slightly effectiveness of peptide vaccine. We investigated the interaction between ovarian clear cell carcinoma cells and peritoneal cells. We showed that the expressions of VEGF, IL-6 and IL-8 elevated and the functions of CD8 possitive T cells (CTL) were decreased. Our results showed that peritoneal dissemination of ovarian carcinoma was immunosuppresive environment.

Research Products

• [Journal Article] GPC3 expression in mouse ovarian cancer induces GPC3-apecific T cell-mediated immune response through M1 macrophages and suppresses tumor growth (2014)
  • Author(s): Luo C, Shibata K, Suzuki S, Kajiyama H, Senga T, Koya Y, Daimon M, Yamashita M, Kikkawa F.
  • Journal Title: Oncol Rep Volume: 32(3) Pages: 913-921
  • Peer Reviewed / Open Access
• [Journal Article] Significant clinical response of progressive recurrent ovarian clear cell carcinoma to glypican-3-derived peptide vaccine therapy: Two case reports. (2013)
  • Author(s): Suzuki S, Shibata K, Kikkawa F, Nakatsura T
  • Journal Title: Hum Vaccin Immunother Volume: 19;10(2) Issue: 2 Pages: 338-343
  • DOI: 10.4161/hv.27217
  • Peer Reviewed
• [Journal Article] ALX1 induces snail expression to promote epithelial-to-mesenchymal transition and invasion of ovarian cancer cells. (2013)
  • Author(s): Yuan H, Kajiyama H, Ito S, Yoshikawa N, Hyodo, Shibata K,Hamaguch M, Kikkawa F, Senga T.
  • Journal Title: Cancer Res Volume: 73(5) Issue: 5 Pages: 1581-1590
  • DOI: 10.1158/0008-5472.can-12-2377
  • Peer Reviewed
• [Journal Article] Diagnostic utility of CD117, CD133, SALL4, OCT4, TCL1 and glypica-3 in malignant germ cell. (2012)
  • Author(s): Trinh DT, Shibata K, Hirisawa T, Umezu T,Mizuno M, Kajiyama H, Kikkawa F.
  • Journal Title: J Obstet Gynaecol Res. Volume: 38(5) Issue: 5 Pages: 841-848
  • DOI: 10.1111/j.1447-0756.2011.01798.x
  • Peer Reviewed
• [Presentation] Effectiveness and immunological analysis in a phase II clinical trial of the GPC3 derived peptide vaccine for ovarian clear cell adenocarcinoma patients (2014)
  • Author(s): Shibata K, Mizuno M, Suzuki S, Mitui H, Kikkawa F
  • Organizer: International Gynecologic Cancer Society
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2014-11-08 – 2014-11-11
• [Presentation] mmunological analysis in a phase II clinical trial of GPC3 derived peptide vaccine for ovarian clear cell adenocarcinoma patients. (2013)
  • Author(s): Shibata K
  • Organizer: he joint symposium of the University of Adelaide and Nagoya
  • Place of Presentation: Adelaide, Australia
• [Presentation] 卵巣明細胞腺癌を対象としたGPC3特異的ペプチドワクチン療法の臨床第Ｉ、II相試験 (2012)
  • Author(s): 柴田清住、鈴木史朗、梶山広明、水野美香、梅津朋和、吉川史隆
  • Organizer: 第６４回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 卵巣明細胞腺癌に対してGlypican-3は有効な免疫療法のターゲットになりうるか？ (2012)
  • Author(s): 鈴木史朗、廣澤友也、柴田清住、吉川史隆
  • Organizer: 第６４回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 卵巣明細胞腺癌を対象としたGlypican-3ペプチドワクチン療法における免疫モニタリング (2012)
  • Author(s): 鈴木史朗、柴田清住、芳川修久、足立学、山田英里、関谷龍一郎、三井寛子、熊澤詔子、梅津朋和、水野美香、梶山広明、吉川史隆、中面哲也
  • Organizer: 第５２回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: グランドプリンスﾎﾃﾙ新高輪
• [Book] 臨床婦人科産科 (2015)
  • Author(s): 柴田清住、吉川史隆
  • Total Pages: 168
  • Publisher: 医学書院
• [Book] 特集 癌免疫療法の最前線 (2014)
  • Author(s): 柴田清住、吉川史隆
  • Total Pages: 8
  • Publisher: 診断と治療社