Therapeutic effects on cancer stem cells using dendritic-cell vaccine pulsed by cancer cells derived from malignant pleural or peritoneal fluid

• Project/Area Number: 26461934
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Tottori University
• Principal Investigator: Tsujitani Shunichi 鳥取大学, 医学部附属病院, 教授 (30188544)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: がん幹細胞 / 樹状細胞 / 免疫回避機構 / 癌性腹膜炎 / ワクチン治療

Outline of Final Research Achievements

Peritoneal dissemination of gastric cancer stem cells and overcoming immune escape were investigated. In 16 patients with malignant ascites, intraperitoneal free cancer cells were obtained by using cell-free and concentrated ascites rein fusion therapy (CART). CD45-EpCAM+ cancer cells were separated from cancer cells obtained by washing the filtration filters. More than 2.4 x 105 cancer cells were obtained in all of the cases. These data suggest that dendritic cell vaccine can be introduced by using cancer cells in malignant ascites. Cultured gastric cancer cell lines MKN45 and MKN74 were sorted by FACS into CD44+ and CD44- cells. Cytotoxic T cells (CTL) from healthy donor co-cultured with CD44+ gastric cancer cells could kill CD44+ gastric cancer cells as well as that CTL co-cultured with CD44- gastric cancer cells could kill CD44- gastric cancer cells. These results indicate that cancer stem cells may be killed by cancer specific immunotherapy using dendritic cell vaccine.

Research Products

• [Journal Article] Gastric cancer treated by endoscopic submucosal dissection or endoscopic mucosal resection in Japan from 2004 through 2006: JGCA nationwide registry conducted in 2013 (2017)
  • Author(s): Tanabe S, Hirabayashi S, Oda I, Ono H, Nashimoto A, Isobe Y, Miyashiro I, Tsujitani S, Seto Y, Fukagawa T, Nunobe S, Furukawa H, Kodera Y, Kaminishi M, Katai H
  • Journal Title: Gastric Cancer Volume: 20 Issue: 5 Pages: 834
  • DOI: 10.1007/s10120-017-0699-4
  • NAID: 40021337993
  • Peer Reviewed
• [Journal Article] Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001–2007) (2017)
  • Author(s): Katai H, Ishikawa T, Akazawa K, Isobe Y, Miyashiro I, Oda I, Tsujitani S, Ono H, Tanabe S, Fukagawa T, Nunobe S, Kakeji Y, Nashimoto A; Registration Committee of the Japanese Gastric Cancer Association
  • Journal Title: Gastric Cancer Volume: 21 Issue: 1 Pages: 144
  • DOI: 10.1007/s10120-017-0716-7
  • NAID: 40021436651
  • Peer Reviewed / Open Access
• [Journal Article] アフェレーシス検体から血中循環癌細胞の分離、培養の試み (2015)
  • Author(s): 征矢良子、田口淳一、永川裕一、岡本正人、辻谷俊一、土田明彦
  • Journal Title: 癌と化学療法 Volume: 42 Pages: 1069-1092
  • Peer Reviewed
• [Journal Article] Prognostic factors related to add-on dendritic cell vaccines on patients with inoperable pancreatic cancer receiving chemotherapy: a multicenter analysis. (2014)
  • Author(s): Kobayashi M, Shimodaira S, Nagai K, Ogasawara M, Takahashi H, Abe H, Tanii M, Okamoto M, Tsujitani S, Yusa S, Ishidao T, Kishimoto J, Shibamoto Y, Nagaya M, Yonemitsu Y; DC Vaccine Study Group at the Japan Society of Innovative Cell Therapy (J-SICT).
  • Journal Title: Cancer Immunol Immunother Volume: 63 Issue: 8 Pages: 797-806
  • DOI: 10.1007/s00262-014-1554-7
  • Peer Reviewed
• [Presentation] Active palliation and new treatment strategy for malignant ascites using KM-CART (2014)
  • Author(s): Matsusaki K, Yoshizawa A, Tsujitani S, Ohta K
  • Organizer: European Society of Medical Oncology (ESMO) 2014
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2014-09-26 – 2014-09-30