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2018 Fiscal Year Research-status Report

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

Research Project

Project/Area Number 17K10603
Research InstitutionWakayama Medical University

Principal Investigator

尾島 敏康  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, 准教授 (10322372)
中村 公紀  和歌山県立医科大学, 医学部, 講師 (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
KeywordsiPS細胞 / 樹状細胞 / がんワクチン / アデノウイルスベクター / 腫瘍抗原 / 細胞傷害性T細胞
Outline of Annual Research Achievements

平成30年度は担癌患者iPS-TAA-DC in vitro刺激で得られたCTLのTAA特異的細胞傷害活性の解析を行った.
本研究はiPS-DC癌ワクチン療法の臨床応用に向けてのpreclinical studyであり,当大学倫理委員会の承認を得ている(approval number 1594, UMIN: 000021106).
6例の大腸癌患者がエントリーした.6例すべての切除標本よりCTOS法を用いて、cell line化に成功し,そのうち4例がCEA蛋白陽性 2例がWT1蛋白陽性であった.4例のCEA陽性大腸癌患者のおのおののiPS-DCにアデノウイルスベクターを用いて遺伝子導入し,その導入効率をFACSにて検討した.のこりの2名は同様にWT1遺伝子を導入し,その発現を確認した.その後,担癌患者6名のおのおののPBMCに対してiPS-TAA-DCのin vitro刺激を3回行い,28日かけてbulk CTLを誘導,その後MACSにてCD8+CTLを選別し,effector細胞とした.Target細胞はCTOS法で得られたcell lineとし,細胞傷害活性をCr release assay法を用いて検討した.結果として,全例にTAA特異的なCTLが誘導され,おのおののcell lineに対して強力な殺腫瘍効果を認めた.現在,テトラマーassayを行い,population数のチェックを行っている.しかし,数回行ったが,明らかなテトラマー陽性細胞は検出できず,現在は抗体を変更したり,assay法を工夫しながら研究を進めているところである.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

平成30年度は担癌患者iPS-TAA-DC in vitro刺激で得られたCTLのTAA特異的細胞傷害活性の解析を行った.結果6例の大腸癌患者よりTAA特異的なCTLが誘導された.6例中4例が初回のCr release assayで作業仮説どうりの結果が得られ,2例も2回目のassayで結果が得られた.計画通りに研究は進んだ考えている.現在そのpopulationの解析を行うためテトラマーassayを行っているが,現時点ではテトラマー陽性細胞はdetectできず,繰り返し研究を行っている.
以上のごとく,おおむね順調に研究は進展していると評価した.

Strategy for Future Research Activity

平成31年度も引き続き,新たな癌患者からのCTOS法を用いたcell lineの作成,iPS-DCの樹立,in vitroでのCTL誘導を行っていく.現在停滞しているテトラマー陽性細胞の検出に関しては,抗体を変更し,行っている.また,これまでは大腸癌でのみCTOS法が成功しており,平成31年度は胃癌患者および膵癌患者からのCTOS法確立を目指す.

Causes of Carryover

今年度末の論文投稿料の使用計画にずれ(年度末の投稿にて支払いが新年度になってしまった)、次年度繰越金が発生しました.

  • Research Products

    (21 results)

All 2019 2018

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 7 results) Presentation (3 results)

  • [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 Pages: e15091

    • DOI

      10.1097/MD.0000000000015091.

    • 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 results.2019

    • 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 Pages: 847-855

    • DOI

      10.18632/oncotarget.26614.

    • 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 trial.2019

    • 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 Pages: 83

    • DOI

      10.1186/s13063-019-3201-2.

    • 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 Pages: in press

    • DOI

      10.1016/j.jviscsurg.2018.12.005.

    • 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 Pages: 201-211

    • DOI

      10.1007/s00262-018-2263-4

    • 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 Pages: in press

    • DOI

      10.1007/s11605-018-3983-7.

    • 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

    • 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 Pages: E1093-E1099

    • DOI

      10.1055/a-0581-9005.

    • 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 Pages: 5267-5273

    • DOI

      10.21873/anticanres.12852.

    • 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 Pages: 334-336

    • DOI

      10.1097/SLE.0000000000000570.

    • Peer Reviewed
  • [Journal Article] Robotic versus laparoscopic gastrectomy with lymph node dissection for gastric cancer: study protocol for a randomized controlled trial.2018

    • 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 Pages: 409

    • DOI

      10.1186/s13063-018-2810-5.

    • 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 Esophagus.2018

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

      Oncology

      Volume: 95 Pages: 116-120

    • DOI

      10.1159/000488861.

    • 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 Pages: 1475-1476

    • DOI

      10.1007/s11605-018-3765-2.

    • Peer Reviewed
  • [Journal Article] Cancer Vaccine Therapy Using Carcinoembryonic Antigen - expressing Dendritic Cells generated from Induced Pluripotent Stem Cells.2018

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

      Scientific Reports

      Volume: 8 Pages: 4569

    • DOI

      10.1038/s41598-018-23120-z.

    • 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 Pages: 935-940

    • DOI

      10.1007/s11605-018-3680-6.

    • 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 Pages: 934

    • DOI

      10.1007/s11605-018-3678-0.

    • 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 Pages: 252-255

    • DOI

      10.1111/ases.12447.

    • 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 Pages: 351-357

    • DOI

      10.1007/s00464-017-5683-x.

    • Peer Reviewed
  • [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
  • [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
  • [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

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Published: 2019-12-27  

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