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Cancer vaccine therapy using iPS-DCs expressing TAA and TGF-beta R

Research Project

Project/Area Number 17K10603
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionWakayama Medical University

Principal Investigator

Ojima Toshiyasu  和歌山県立医科大学, 医学部, 講師 (60448785)

Co-Investigator(Kenkyū-buntansha) 中森 幹人  和歌山県立医科大学, 医学部, 非常勤講師 (10322372)
中村 公紀  和歌山県立医科大学, 医学部, 准教授 (80364090)
山上 裕機  和歌山県立医科大学, 医学部, 教授 (20191190)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsiPS細胞 / 樹状細胞 / 腫瘍免疫 / 細胞傷害性Tリンパ球 / 癌ワクチン / 免疫遺伝子治療 / がんワクチン / CTOS / アデノウイルスベクター / 腫瘍抗原 / 細胞傷害性T細胞 / 腫瘍抗原遺伝子 / TGF-betaR遺伝子
Outline of Final Research Achievements

We investigated whether genetically modified human induced pluripotent stem cell (iPS)-derived dendritic cells (hiPSDCs) expressing tumor associated antigen (TAA) could induce TAA-specific cytotoxic T cells in patients with gastrointestinal cancer. We differentiated hiPSDCs from iPSCs of six patients with colorectal cancer. The surface marker expression, cytokine secretion and migratory capacity of the hiPSDCs were equivalent to those of healthy donors. Next, we transduced TAA cDNA into the hiPSDCs derived from colorectal cancer patients. Cytotoxic T cells activated by hiPSDCs-TAA exhibited TAA-specific cytotoxic activity against the cancer tissue-originated spheroid cells expressing TAA.

Academic Significance and Societal Importance of the Research Achievements

Immune check point inhibitorが着目され,癌免疫治療の有用性は明らかとなったが,それでも有効な症例は限られている.私達は,iPS細胞は,癌研究,なかでも癌免疫治療の分野において有用な材料であると考える.私達が目指すテーラーメードiPSDCs癌ワクチン療法は,臨床応用されれば,癌免疫療法においてこれまでのDCワクチン療法の問題点を克服する新規precision medicineに位置づけられるものと考える.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (39 results)

All 2020 2019 2018 2017

All Journal Article (29 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 29 results,  Open Access: 10 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Anticancer effects of chemokine-directed antigen delivery to a cross-presenting dendritic cell subset with immune checkpoint blockade2020

    • Author(s)
      Mizumoto Y, Hemmi H, Katsuda M, Miyazawa M, Kitahata Y, Miyamoto A, Nakamori M, Ojima T, Matsuda K, Nakamura M, Hayata K, Fukuda-Ohta Y, Sugiyama M, Ohta T, Orimo T, Okura S, Sasaki I, Tamada K, Yamaue H, Kaisho T.
    • Journal Title

      British Journal of Cancer

      Volume: 122 Issue: 8 Pages: 1185-1193

    • DOI

      10.1038/s41416-020-0757-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Laparoscopic Roux-en-Y reconstruction using conventional linear stapler in robotic total gastrectomy for gastric cancer.2019

    • Author(s)
      Ojima T, Nakamura M, Hayata K, Yamaue H.
    • Journal Title

      Surg Oncol.

      Volume: 33 Pages: 9-10

    • DOI

      10.1016/j.suronc.2019.12.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic Billroth I Gastroduodenostomy in Robotic Distal Gastrectomy for Gastric Cancers: Fusion Surgery.2019

    • Author(s)
      Ojima T, Nakamura M, Hayata K, Nakamori M, Kitadani J, Katsuda M, Fukuda N, Yamaue H.
    • Journal Title

      Surg Laparosc Endosc Percutan Tech.

      Volume: 29 Issue: 6 Pages: 520-523

    • DOI

      10.1097/sle.0000000000000720

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Robotic distal gastrectomy with D2 lymphadenectomy for gastric cancer in a patient with situs inversus totalis.2019

    • Author(s)
      Ojima T, Nakamura M, Nakamori M, Yamaue H.
    • Journal Title

      Surg Oncol.

      Volume: 30 Pages: 98-99

    • DOI

      10.1016/j.suronc.2019.06.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of CEACAM1 is associated with poor prognosis and peritoneal dissemination of patients with gastric cancer.2019

    • Author(s)
      Takeuchi A, Yokoyama S, Nakamori M, Nakamura M, Ojima T, Yamaguchi S, Mitani Y, Shively JE, Yamaue H.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 12702-12702

    • DOI

      10.1038/s41598-019-49230-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Robotic total gastrectomy with Roux-en-Y reconstruction for gastric cancer (with video).2019

    • Author(s)
      Ojima T, Hara I, Yamaue H.
    • Journal Title

      J Visc Surg.

      Volume: 156 Issue: 5 Pages: 461-462

    • DOI

      10.1016/j.jviscsurg.2019.06.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy.2019

    • Author(s)
      Katsuda M, Miyazawa M, Ojima T, Katanuma A, Hakamada K, Sudo K, Asahara S, Endo I, Ueno M, Hara K, Yamada S, Fujii T, Satoi S, Ioka T, Ohira M, Akahori T, Kitano M, Nagano H, Furukawa M, Adachi T, Yamaue H.
    • Journal Title

      Trials

      Volume: 20 Issue: 1 Pages: 242-242

    • DOI

      10.1186/s13063-019-3332-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Robotic radical lymphadenectomy without touching the pancreas during gastrectomy for gastric cancer.2019

    • Author(s)
      Ojima T, Nakamura M, Nakamori M, Hayata K, Katsuda M, Maruoka S, Yamaue H.
    • Journal Title

      Medicine

      Volume: 98 Issue: 13 Pages: e15091-e15091

    • DOI

      10.1097/md.0000000000015091

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Triplet chemotherapy with docetaxel, cisplatin and S-1 for unresectable advanced squamous cell carcinoma of the esophagus: phase I/II trial results2019

    • Author(s)
      Ojima T, Nakamura M, Nakamori M, Katsuda M, Hayata K, Kitadani J, Maruoka S, Shimokawa T, Yamaue H.
    • Journal Title

      Oncotarget

      Volume: 10 Issue: 8 Pages: 847-855

    • DOI

      10.18632/oncotarget.26614

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Triangulating stapling vs functional end-to-end stapling for cervical esophagogastric anastomosis after esophagectomy for thoracic esophageal cancer: study protocol for a randomized controlled trial2019

    • Author(s)
      Tsuji T, Ojima T, Nakamori M, Nakamura M, Katsuda M, Hayata K, Kitadani J, Maruoka S, Shimokawa T, Yamaue H.
    • Journal Title

      Trials

      Volume: 20 Issue: 1 Pages: 83-83

    • DOI

      10.1186/s13063-019-3201-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Robotic complete lymphadenectomy at the splenic hilum during total gastrectomy for advanced gastric cancer (with video).2019

    • Author(s)
      Ojima T, Hayata K, Yamaue H.
    • Journal Title

      Journal of Visceral Surgery

      Volume: in press Issue: 2 Pages: 173-174

    • DOI

      10.1016/j.jviscsurg.2018.12.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory functions of PD-L1 and PD-L2 in the regulation of anti-tumor immunity in murine tumor microenvironment.2019

    • Author(s)
      Umezu D, Okada N, Sakoda Y, Adachi K, Ojima T, Yamaue H, Eto M, Tamada K.
    • Journal Title

      Cancer Immunology and Immunotheraoy

      Volume: 68 Issue: 2 Pages: 201-211

    • DOI

      10.1007/s00262-018-2263-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Conversion Surgery for Gastric Cancer with Peritoneal Metastasis Based on the Diagnosis of Second-Look Staging Laparoscopy.2019

    • Author(s)
      Nakamura M, Ojima T, Nakamori M, Katsuda M, Tsuji T, Hayata K, Kato T, Yamaue H.
    • Journal Title

      Journal of Gastrointestinal Surgery

      Volume: in prss Issue: 9 Pages: 1758-1766

    • DOI

      10.1007/s11605-018-3983-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] In Vivo Antigen Delivery to Dendritic Cells-A Novel Peptide Vaccine for Cancer Therapy.2018

    • Author(s)
      Mizumoto Y, Katsuda M, Miyazawa M, Kitahata Y, Miyamoto A, Nakamori M, Ojima T, Matsuda K, Hemmi H, Tamada K, Kaisho T, Yamaue H.
    • Journal Title

      Gan To Kagaku Ryoho.

      Volume: 45 Pages: 1469-1471

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endoscopic treatment of esophageal fistulas after esophagectomy with injection of an alpha-cyanoacrylate monomer: a phase II study.2018

    • Author(s)
      Ojima T, Nakamura M, Nakamori M, Katsuda M, Hayata K, Tsuji T, Maruoka S, Yamaue H.
    • Journal Title

      Endoscopy International Open

      Volume: 6 Issue: 09 Pages: E1093-E1099

    • DOI

      10.1055/a-0581-9005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neoadjuvant Chemotherapy with Docetaxel, Cisplatin and S-1 for Resectable Advanced Esophageal Cancer.2018

    • Author(s)
      Hayata K, Ojima T, Nakamori M, Nakamura M, Katsuda M, Kitadani J, Takeuchi A, Tabata H, Maruoka S, Yamaue H.
    • Journal Title

      Anticancer Research

      Volume: 38 Issue: 9 Pages: 5267-5273

    • DOI

      10.21873/anticanres.12852

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reinforced Stapling Technique for Reconstruction After Laparoscopic Distal Gastrectomy.2018

    • Author(s)
      Ojima T, Nakamura M, Hayata K, Nakamori M, Yamaue H.
    • Journal Title

      Surgical Laparoscopy Endoscopy Percutaneous Techniques

      Volume: 28 Issue: 5 Pages: 334-336

    • DOI

      10.1097/sle.0000000000000570

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Robotic versus laparoscopic gastrectomy with lymph node dissection for gastric cancer: study protocol for a randomized controlled trial2018

    • Author(s)
      Ojima T, Nakamura M, Nakamori M, Hayata K, Katsuda M, Kitadani J, Maruoka S, Shimokawa T, Yamaue H.
    • Journal Title

      Trials

      Volume: 19 Issue: 1 Pages: 409-409

    • DOI

      10.1186/s13063-018-2810-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phase I/II Trial of Chemotherapy with Docetaxel, Cisplatin, and S-1 for Unresectable Advanced Squamous Cell Carcinoma of the Esophagus2018

    • Author(s)
      Ojima T, Nakamura M, Nakamori M, Katsuda M, Hayata K, Maruoka S, Shimokawa T, Yamaue H.
    • Journal Title

      Oncology

      Volume: 95 Issue: 2 Pages: 116-120

    • DOI

      10.1159/000488861

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fundoplication with 180-Degree Wrap During Esophagogastrostomy After Robotic Proximal Gastrectomy for Early Gastric Cancer.2018

    • Author(s)
      Ojima T, Nakamori M, Nakamura M, Hayata K, Maruoka S, Yamaue H.
    • Journal Title

      Journal of Gastrointestinal Surgery

      Volume: 22 Issue: 8 Pages: 1475-1476

    • DOI

      10.1007/s11605-018-3765-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cancer Vaccine Therapy Using Carcinoembryonic Antigen - expressing Dendritic Cells generated from Induced Pluripotent Stem Cells2018

    • Author(s)
      Kitadani Junya、Ojima Toshiyasu、Iwamoto Hiromitsu、Tabata Hirotaka、Nakamori Mikihito、Nakamura Masaki、Hayata Keiji、Katsuda Masahiro、Miyajima Masayasu、Yamaue Hiroki
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 4569-4569

    • DOI

      10.1038/s41598-018-23120-z

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Laparoscopic and Endoscopic Cooperative Surgery Versus Endoscopic Submucosal Dissection for the Treatment of Low-Risk Tumors of the Duodenum.2018

    • Author(s)
      Ojima T, Nakamori M, Nakamura M, Hayata K, Katsuda M, Takifuji K, Yamaue H.
    • Journal Title

      Journal of Gastrointestinal Surgery

      Volume: 22 Issue: 5 Pages: 935-940

    • DOI

      10.1007/s11605-018-3680-6

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prevention of Internal Hernia During Robotic Total Gastrectomy for Gastric Cancer.2018

    • Author(s)
      Ojima T, Nakamura M, Nakamori M, Hayata K, Katsuda M, Tsuji T, Maruoka S, Yamaue H.
    • Journal Title

      Journal of Gastrointestinal Surgery

      Volume: 22 Issue: 5 Pages: 934-934

    • DOI

      10.1007/s11605-018-3678-0

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Usefulness of indocyanine green fluorescence imaging: A case of laparoscopic distal gastrectomy after distal pancreatectomy with splenectomy.2018

    • Author(s)
      Maruoka S, Ojima T, Nakamori M, Nakamura M, Hayata K, Katsuda M, Tsuji T, Yamaue H.
    • Journal Title

      Asian Journal of Endoscopic Surgery

      Volume: 11 Issue: 3 Pages: 252-255

    • DOI

      10.1111/ases.12447

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic and endoscopic cooperative surgery is a feasible treatment procedure for intraluminal gastric gastrointestinal stromal tumors compared to endoscopic intragastric surgery.2018

    • Author(s)
      Ojima T, Nakamura M, Nakamori M, Takifuji K, Hayata K, Katsuda M, Takei Y, Yamaue H.
    • Journal Title

      Surgical Endoscopy

      Volume: 32 Issue: 1 Pages: 351-357

    • DOI

      10.1007/s00464-017-5683-x

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Internal Hernia After Laparoscopic Total Gastrectomy for Gastric Cancer.2017

    • Author(s)
      Ojima T, Nakamori M, Nakamura M, Katsuda M, Hayata K, Kato T, Tsuji T, Yamaue H.
    • Journal Title

      Surgical Laparoscopy Endoscopy Percutaneous Technique

      Volume: 27 Issue: 6 Pages: 470-473

    • DOI

      10.1097/sle.0000000000000481

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer2017

    • Author(s)
      Ojima T, Nakamori M, Nakamura M, Katsuda M, Hayata K, Kato T, Kitadani J, Tabata H, Takeuchi A, Yamaue H.
    • Journal Title

      British Journal of Surgery

      Volume: in press Issue: 8 Pages: 1003-1009

    • DOI

      10.1002/bjs.10548

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Circular stapling versus triangulating stapling for the cervical esophagogastric anastomosis after esophagectomy in patients with thoracic esophageal cancer: A prospective, randomized, controlled trial.2017

    • Author(s)
      Hayata K, Nakamori M, Nakamura M, Ojima T, Iwahashi M, Katsuda M, Tsuji T, Kato T, Kitadani J, Takeuchi A, Tabata H, Yamaue H.
    • Journal Title

      Surgery.

      Volume: in press Issue: 1 Pages: 131-138

    • DOI

      10.1016/j.surg.2017.01.013

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Laparoscopic Gastrojejunostomy for Patients with Unresectable Gastric Cancer with Gastric Outlet Obstruction.2017

    • Author(s)
      Ojima T, Nakamori M, Nakamura M, Katsuda M, Hayata K, Yamaue H.
    • Journal Title

      J Gastrointest Surg.

      Volume: in press Issue: 8 Pages: 1220-1225

    • DOI

      10.1007/s11605-017-3387-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] iPS細胞由来樹状細胞を用いた癌ワクチン療法 -Neoantigen解析-2020

    • Author(s)
      尾島 敏康 岩本 博光 北谷 純也  丸岡 慎平 田端 宏尭 山上 裕機
    • Organizer
      第53回制癌剤適応研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cancer Vaccine Therapy using iPS-derived Dendritic Cells2019

    • Author(s)
      Toshiyasu Ojima
    • Organizer
      The 10 th Meeting of Asian Cellular Therapy Organization
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS細胞由来樹状細胞を用いたテーラーメード癌ワクチン療法の現状と未来2018

    • Author(s)
      尾島敏康 岩本博光 北谷純也 田端宏尭 出口真彰 中森幹人 中村公紀 勝田将裕 早田啓治 丸岡慎平 山上裕機
    • Organizer
      第31回日本バイオセラピー学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cancer vaccine therapy using iPS-derived dendritic cells Second Department of Surgery, Wakayama medical university, school of medicine2018

    • Author(s)
      尾島敏康 岩本博光 北谷純也 田端宏尭 出口真彰 中森幹人 中村公紀 勝田将裕 早田啓治 丸岡慎平 山上裕機
    • Organizer
      第56回日本癌治療学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] iPS細胞由来樹状細胞を用いた癌ワクチン療法2018

    • Author(s)
      尾島敏康 岩本博光 北谷純也 田端宏尭 出口真彰 丸岡慎平 中森幹人 中村公紀 勝田将裕 早田啓治  山上裕機
    • Organizer
      第119回日本外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] iPS細胞由来樹状細胞を用いた テーラーメード癌ワクチン療法2018

    • Author(s)
      尾島敏康 岩本博光 北谷純也 田端宏尭 出口真彰 山上裕機
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] iPS細胞由来樹状細胞を用いた癌ワクチン療法2018

    • Author(s)
      尾島敏康 岩本博光 北谷純也 田端宏尭  出口真彰 中森幹人 中村公紀 勝田将裕  早田啓治 山上裕機
    • Organizer
      第118回日本外科学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cancer vaccine therapy using iPS-derived dendritic cells2017

    • Author(s)
      尾島敏康 岩本博光 北谷純也 田端宏尭  出口真彰 中森幹人 中村公紀 勝田将裕  早田啓治 山上裕機
    • Organizer
      第30回日本バイオセラピー学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cancer Vaccine Therapy using iPS-derived Dendritic Cells2017

    • Author(s)
      尾島敏康
    • Organizer
      第28回日本消化器癌発生学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Feasibility of Cancer Vaccine Therapy using Dendritic Cells Generated from Induced Pluripotent Stem Cells Expressing Carcinoembryonic Antigen2017

    • Author(s)
      Toshiyasu Ojima, Junya Kitadani, Hiromitsu Iwamoto, Mikihito Nakamori, Masaki Nakamura, and Hiroki Yamaue
    • Organizer
      ASCO 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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