Establishment of monitoring method for Ad-REIC-based therapeutic effects on cancer using the newly developed anti-REIC antibody that recognizes the cancer specific REIC conformation

• Project/Area Number: 16K18440
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: Okayama University
• Principal Investigator: Kinoshita Rie 岡山大学, 医歯薬学総合研究科, 助教 (40518297)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: REIC / 遺伝子治療 / がん / がん抑制遺伝子 / モノクローナル抗体 / ELISA / 癌 / 蛋白質

Outline of Final Research Achievements

Reduced expression in immortalized cells (REIC) is a tumor suppressor gene and has been studied as a promising therapeutic gene for cancer gene therapy. Intratumoral injection of adenovirus vector carrying the human REIC (Ad-REIC) elicits cancer cell-specific apoptosis and anti-cancer immune responses. In addition, Ad-REIC gene therapy resulted in complete response in the case of metastatic castration-resistant prostate cancer patient. We obtained various anti-REIC monoclonal antibodies and developed a sandwich ELISA method for measuring the REIC protein concentration in the human blood. Using this assay, we have successfully developed the method for monitoring cancer treatment with Ad-REIC.

Research Products

• [Journal Article] Signal Diversity of Receptor for Advanced Glycation End Products (2017)
  • Author(s): Sakaguchi M, Kinoshita R, Putranto EW, Ruma IMW, Sumardika IW, Youyi C, Tomonobu N, Yamamoto KI, Murata H.
  • Journal Title: Acta Medica Okayama Volume: 71 Issue: 6 Pages: 459-465
  • DOI: 10.18926/AMO/55582
  • NAID: 120006370709
  • URL: https://ousar.lib.okayama-u.ac.jp/55582
  • Peer Reviewed / Open Access
• [Journal Article] Exogenous DKK-3/REIC inhibits Wnt/β-catenin signaling and cell proliferation in human kidney cancer KPK1 (2017)
  • Author(s): Xu Jiaqi、Sadahira Takuya、Kinoshita Rie、Li ShunAi、Huang Peng、Wada Koichiro、Araki Motoo、Ochiai Kazuhiko、Noguchi Hirofumi、Sakaguchi Masakiyo、Nasu Yasutomo、Watanabe Masami
  • Journal Title: Oncology Letters Volume: 14 Pages: 5638-5642
  • DOI: 10.3892/ol.2017.6833
  • Peer Reviewed / Open Access
• [Journal Article] ｂ-1,3-galactosyl-O-glycosyl-glycoprotein ｂ-1,6-N-acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility. (2017)
  • Author(s): Sumardika I Wayan、Youyi Chen、Kondo Eisaku、Inoue Yusuke、Ruma I Made Winarsa、Murata Hitoshi、Kinoshita Rie、Yamamoto Ken-Ichi、Tomida Shuta、Shien Kazuhiko、Satoh Hiroki、Yamauchi Akira、Futami Junichiro、Putranto Endy Widya、Hibino Toshihiko、Toyooka Shinichi、Nishibori Masahiro、Sakaguchi Masakiyo
  • Journal Title: Oncology Reserch Volume: in press Issue: 3 Pages: 431-444
  • DOI: 10.3727/096504017x15031557924123
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of tumor suppressor REIC/Dkk-3 by a newly improved adenovirus vector with insertion of an hTERT promoter at the 3’-side of the transgene. (2017)
  • Author(s): Putranto EW, Kinoshita R, Watanabe M, Sadahira T, Murata H, Yamamoto KI, Futami J, Kataoka K, Inoue Y, Ruma IM, Sumardika IW, Youyi C, Kubo M, Sakaguchi Y, Saito K, Nasu Y, Kumon H, Huh NH, and Sakaguchi M.
  • Journal Title: Oncol. Lett. Volume: 14 Issue: 1 Pages: 1041-1048
  • DOI: 10.3892/ol.2017.6201
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Robust cancer-specific gene expression by a novel cassette with hTERT and CMV promoter elements. (2017)
  • Author(s): Sakaguchi M, Sadahira T, Ueki H, Kinoshita R, Murata H, Yamamoto KI, Futami J, Nasu Y, Ochiai K, Kumon H, Huh NH, Watanabe M.
  • Journal Title: Oncology Reports Volume: 38 Issue: 2 Pages: 1108-1114
  • DOI: 10.3892/or.2017.5710
  • Peer Reviewed / Open Access
• [Presentation] S100A8/A9を標的としたがん転移制御法の開発 (2017)
  • Author(s): 木下理恵 村田等 山本健一 許南浩 日比野利彦 阪口政清
  • Organizer: 日本組織培養学会第90回大会
• [Presentation] 転移先臓器を感知する受容体 (2017)
  • Author(s): 阪口政清 木下理恵 村田等 山本健一 日比野利彦 許南浩
  • Organizer: 日本組織培養学会第90回大会
• [Presentation] ミトコンドリア呼吸鎖複合体への作用を介したSARM1の神経細胞死誘導 (2017)
  • Author(s): 村田等 西川茜 山本健一 木下理恵 阪口政清
  • Organizer: 日本組織培養学会第90回大会
• [Presentation] Development of novel biologics for cancer metastasis via prevention of extracellular S100A8/A9 function (2017)
  • Author(s): Rie Kinoshita, Akira Yamauchi, Hiroki Sato, Yusuke Inoue, Kazuhiko Shien, Shuta Tomida, Hitoshi Murata, Shinichi Toyooka, Eisaku Kondo and Masakiyo Sakaguchi
  • Organizer: The 76th Annual Meeting of the Japanese Cancer Association
• [Presentation] Development of a novel biologics for suppression of S100A8/A9-induced cancer metastasis (2016)
  • Author(s): Rie Kinoshita, Hitoshi Murata, Yusuke Inoue, Eisaku Kondo, Nam-Ho Huh, Masakiyo Sakaguchi
  • Organizer: The 75th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-08
• [Patent(Industrial Property Rights)] REIC/Dkk-3タンパク質を有効成分として含むTGFβ阻害剤 (2017)
  • Inventor(s): 木下 理恵、二見 淳一郎、公文 裕巳
  • Industrial Property Rights Holder: 木下 理恵、二見 淳一郎、公文 裕巳
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Overseas
• [Patent(Industrial Property Rights)] 活性構造のREIC/Dkk-3タンパク質を特異的に認識して結合する抗体、及び該抗REIC/Dkk-3抗体を用いた癌治療のモニタリング (2016)
  • Inventor(s): 木下 理恵、 二見 淳一郎、公文 裕巳
  • Industrial Property Rights Holder: 国立大学法人 岡山大学、桃太郎源株式会社
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-09-27
  • Overseas
• [Patent(Industrial Property Rights)] REIC/Dkk-3タンパク質を有効成分として含むTGFβ阻害剤 (2016)
  • Inventor(s): 木下 理恵、 二見 淳一郎、公文 裕巳
  • Industrial Property Rights Holder: 国立大学法人 岡山大学、桃太郎源株式会社
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-121187
  • Filing Date: 2016-06-17