A novel strategy for ubiquitin-fusion gene transduced dendritic cell vaccine in the control of the constituents of the proteasome

• Project/Area Number: 26861095
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Wakayama Medical University
• Principal Investigator: Miyazawa Motoki 和歌山県立医科大学, 医学部, 助教 (90549734)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: プロテアソーム / メソセリン / 樹状細胞ワクチン / ユビキチン

Outline of Final Research Achievements

Immature dendritic cells contains the constitutive proteasome, however, mature dendritic cells differentiated from immature dendritic cells exposed with inflammatory mediator such as interferon-gamma contains immunoproteasome (ip) derived from immature dendritic cells. The inhibition of the immunoproteasome in mature dendritic cells using small interfering RNA transfection targeting the 3 inducible ip subunits might help to induce antigen-specific cytotoxic T lymphocytes. In this study, I performed basic research about anti-tumor immune response targeting mesothelin which is tumor associated antigen of pancreatic ductal carcinoma, and using dendritic cells transduced with mesothelin gene fused with ubiquitin gene which is a degradation signal of proteasome.

Research Products

• [Journal Article] Pancreatic neck cancer has specific and oncologic characteristics regardingportal vein invasion and lymph node metastasis. (2016)
  • Author(s): Hirono S, Kawai M, Okada K, Miyazawa M, Shimizu A, Kitahata Y, Ueno M, Yamaue H.
  • Journal Title: Surgery Volume: 159 Issue: 2 Pages: 426-40
  • DOI: 10.1016/j.surg.2015.07.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preoperative evaluation of the confluent drainage veins to the gastrocolic trunk of Henle: understanding the surgical vascular anatomy duringpancreaticoduodenectomy. (2015)
  • Author(s): Miyazawa M, Kawai M, Hirono S, Okada K, Shimizu A, Kitahata Y, Yamaue H.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 22 Issue: 5 Pages: 386-391
  • DOI: 10.1002/jhbp.205
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Randomized phase II/III clinical trial of elpamotide forpatients with advanced pancreatic cancer: PEGASUS-PC Study. (2015)
  • Author(s): Yamaue H, Tsunoda T, Tani M, Miyazawa M, Yamao K, Mizuno N, Okusaka T, Ueno H,Boku N, Fukutomi A, Ishii H, Ohkawa S, Furukawa M, Maguchi H, Ikeda M, Togashi Y,Nishio K, Ohashi Y.
  • Journal Title: Cancer Sci. Volume: 106 Issue: 7 Pages: 883-890
  • DOI: 10.1111/cas.12674
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preoperative cholangitis during biliary drainage increases the incidence of postoperative severe complications after pancreaticoduodenectomy (2014)
  • Author(s): Yuji Kitahata, Manabu Kawai, Masaji Tani, et al.
  • Journal Title: The American Journal of Surgery Volume: 208 Issue: 1 Pages: 1-10
  • DOI: 10.1016/j.amjsurg.2013.10.021
  • Peer Reviewed / Open Access
• [Journal Article] Indication for the use of an interposed graft during portal vein and/or superior mesenteric vein reconstruction in pancreatic resection based on perioperative outcomes (2014)
  • Author(s): Seiko Hirono, Manabu Kawai, Masaji Tani, Ken-ichi Okada, Motoki Miyazawa, Atsushi Shimizu, Hiroki Yamaue
  • Journal Title: Langenbeck Arch Surg Volume: 未 Issue: 4 Pages: 461-471
  • DOI: 10.1007/s00423-014-1182-x
  • Peer Reviewed / Open Access
• [Journal Article] Predicting factors for unresectability in patients with pancreatic ductal adenocarcinoma. (2014)
  • Author(s): Okada K, Kawai M, Tani M, Hirono S, Miyazawa M, Shimizu A, Kitahata Y, Yamaue H.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 21 Issue: 9 Pages: 648-653
  • DOI: 10.1002/jhbp.109
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Randomized clinical trial of isolated Roux-en-Y versus conventional reconstruction after pancreaticoduodenectomy. (2014)
  • Author(s): Tani M, Kawai M, Hirono S, Okada KI, Miyazawa M, Shimizu A, Kitahata Y, Yamaue H.
  • Journal Title: Br J Surg. Volume: 101 Issue: 9 Pages: 1084-1091
  • DOI: 10.1002/bjs.9544
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preservation of the left gastric artery on the basis of anatomical features in patients undergoing distal pancreatectomy with celiac axis en-bloc resection (DP-CAR). (2014)
  • Author(s): Okada K, Kawai M, Tani M, Hirono S, Miyazawa M, Shimizu A, Kitahata Y, Yamaue H.
  • Journal Title: World J Surg. Volume: 38 Issue: 11 Pages: 2980-2985
  • DOI: 10.1007/s00268-014-2702-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A replaced right hepatic artery adjacent to pancreatic carcinoma should be divided to obtain R0 resection in pancreaticoduodenectomy. (2014)
  • Author(s): Okada K, Kawai M, Hirono S, Miyazawa M, Shimizu A, Kitahata Y, Tani M, Yamaue H.
  • Journal Title: Langenbecks Arch Surg. Volume: 400 Issue: 1 Pages: 57-65
  • DOI: 10.1007/s00423-014-1255-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Dendritic cell vaccine transduced with ubiquitin-mesothelin fusion gene for pancreatic cancer (2017)
  • Author(s): Motoki Miyazawa, Toshiyasu Ojima, Masahiro Katsuda, Manabu Kawai, Seiko Hirono, Ken-ichi Okada, Atsushi Shimizu, Yuji Kitahata, Hiroki Yamaue
  • Organizer: The Joint Conference of IAP & JPS & AOPA
  • Place of Presentation: 仙台国際センター
  • Int'l Joint Research
• [Presentation] 切除不能膵癌に対する新規ペプチドワクチン療法- 第I/II相臨床試験 - (2015)
  • Author(s): 宮澤基樹， 勝田将裕， 川井 学， 廣野誠子， 岡田健一， 清水敦史， 北畑裕司，尾島敏康， 水本有紀， 北谷純也， 津村亜矢子， 和田聡， 山上裕機
  • Organizer: 第28回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 川越市
  • Year and Date: 2015-12-04
  • Int'l Joint Research
• [Presentation] 進行膵癌に対する化学療法を併用した新規がんペプチドワクチンの臨床研究 (2015)
  • Author(s): 宮澤基樹， 勝田将裕， 川井 学， 廣野誠子， 岡田健一， 清水敦史， 北畑裕司， 水本有紀， 北谷純也， 津村亜矢子， 和田聡， 山上裕機
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2015-10-31
  • Int'l Joint Research
• [Presentation] Dendritic cells adenovirally-transduced with full-length mesothelin cDNA elicit mesothelin-specific cytotoxicity against pancreatic cancer cell lines in vitro (2015)
  • Author(s): M. Miyazawa, T. Ojima, M. Kawai, S. Hirono, K. Okada, A. Shimizu, Y. Kitahata, and H. Yamaue
  • Organizer: PCCA and IAP meeting 2015
  • Place of Presentation: Shanghai, China
  • Year and Date: 2015-08-27
  • Int'l Joint Research
• [Presentation] 膵癌ペプチドワクチン療法臨床試験の現状と展望 (2014)
  • Author(s): 宮澤基樹
  • Organizer: 第27回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 大阪府 大阪市
  • Year and Date: 2014-12-04
• [Presentation] Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer (2014)
  • Author(s): Motoki Miyazawa
  • Organizer: 2014 APA/JPS Meeting
  • Place of Presentation: Hawaii USA
  • Year and Date: 2014-11-07 – 2014-11-08
• [Presentation] 標準療法不応膵癌に対するTS-1隔日投与法併用ペプチドワクチン療法 (2014)
  • Author(s): 宮澤基樹
  • Organizer: 第52回日本癌治療学会学術集会
  • Place of Presentation: 神奈川県 横浜市
  • Year and Date: 2014-08-28
• [Presentation] 膵癌に対するペプチドワクチン療法の開発 (2014)
  • Author(s): 宮澤基樹
  • Organizer: 第69回日本消化器外科学会総会
  • Place of Presentation: 福島県 郡山市
  • Year and Date: 2014-07-18