Investigation of the mechanisms of personalized-cancer vaccination by REIC/Dkk-3 based gene therapy.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390382
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Okayama University
• Principal Investigator: KUMON Hiromi 岡山大学, 医歯(薬)学総合研究科, 教授 (30144760)
• Co-Investigator(Kenkyū-buntansha): HUH Namho 岡山大学, 大学院・医歯薬学総合研究科, 教授 (70142023) ; WATANABE Masami 岡山大学, 岡山大学病院, 准教授 (70444677) ; SAKAGUCHI Masakiyo 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70379840) ; KAKU Haruki 岡山大学, 岡山大学病院, 講師 (60346426) ; UEKI Hideo 岡山大学, 医学部, 技術専門職員 (90537218)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 遺伝子治療 / 癌ワクチン / 骨髄系免疫抑制細胞 / REIC/Dkk3

Research Abstract

In situ gene therapy with tumor suppressor, REIC/Dkk-3, induces cancer-specific apoptosis and activation of anti-cancer immune. The combined effects seem to be important for the therapeutic outcomes of personalized-cancer vaccination. In this study, we elucidated that the suppressive effect of REIC/Dkk-3 on the differentiation of MDSC and the following CTL activation are important for the mechanism of the personalized-cancer vaccination.

Research Products

• [Journal Article] A novel gene expression system strongly enhances the anticancer effects of a REIC/Dkk-3-encoding adenoviral vector (2014)
  • Author(s): Watanabe M., Sakaguchi M., Kinoshita R., Kaku H., Ariyoshi Y., Ueki H., Tanimoto R., Ebara S., Ochiai K., Futami J., Li SA., Huang P., Nasu Y., Huh NH., Kumon H
  • Journal Title: Oncology Reports Volume: 31巻 Pages: 1089-95
  • DOI: 10.3892/or.2013.2958
  • Peer Reviewed
• [Journal Article] Adenovirus-mediated REIC/Dkk-3 gene therapy : development of an autologous cancer vaccination therapy (2014)
  • Author(s): Watanabe M., Nasu Y., Kumon H
  • Journal Title: Oncology Letters Volume: 7巻 Pages: 595-601
  • DOI: 10.3892/ol.2013.1777
  • Peer Reviewed
• [Journal Article] Preclinical biodistribution and safety study of reduced expression in immortalized cells/Dickkopf-3-encoding adenoviral vector for prostate cancer gene therapy (2012)
  • Author(s): Sugimoto M., Watanabe M., Kaku H., Li SA., Noguchi H., Ueki H., Sakaguchi M., Huh NH., Nasu Y., Kumon H
  • Journal Title: Oncol Rep Volume: 28巻 Pages: 1645-1652
  • DOI: 10.3892/or.2012.2001
  • Peer Reviewed
• [Journal Article] REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer (2012)
  • Author(s): Hirata T., Watanabe M., Kaku H., Kobayashi Y., Yamada H., Sakaguchi M., Takei K., Huh NH., Nasu Y., Kumon H
  • Journal Title: Int J Oncol Volume: 41巻 Pages: 559-564
  • DOI: 10.3892/ijo.2012.1503
  • Peer Reviewed
• [Journal Article] Preclinical safety and efficacy of in situ REIC/Dkk-3 gene therapy for prostate cancer (2012)
  • Author(s): Kawauchi K., Watanabe M., Kaku H., Huang P., Sasaki K., Sakaguchi M., Ochiai K., Huh NH., Nasu Y., Kumon H
  • Journal Title: Acta Med Okayama Volume: 66巻 Pages: 7-16
  • URL: http://escholarship.lib.okayama-u.ac.jp/amo/vol66/iss1
  • Peer Reviewed
• [Journal Article] Partial sensitization of human bladder cancer cells to a gene-therapeutic adenovirus carrying REIC/Dkk-3 by downregulation of BRPK/PINK1 (2012)
  • Author(s): Jin Y., Murata H., Sakaguchi M., Kataoka K., Watanabe M., Nasu Y., Kumon H., Huh NH
  • Journal Title: Oncol Rep Volume: 27巻 Pages: 695-699
  • DOI: 10.3892/or.2011.1543
  • Peer Reviewed
• [Journal Article] Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1 (2011)
  • Author(s): Ochiai K., Watanabe M., Ueki H., Huang P., Fujii Y., Nasu Y., Noguchi H., Hirata T., Sakaguchi M., Huh NH., Kashiwakura Y., Kaku H., Kumon H
  • Journal Title: Biochem Biophys Res Commun Volume: 412巻 Pages: 391-395
  • DOI: 10.1016/j.bbrc.2011.07.109
  • Peer Reviewed
• [Presentation] Immunomodulation and anti-cancer activity of REIC/Dkk-3 protein (2013)
  • Author(s): Huang P, et al
  • Organizer: European Society of Gene and Cell Therapy
  • Place of Presentation: Madrid Spain
  • Year and Date: 2013-10-26
• [Presentation] Ad-REIC/Dkk-3(REIC expressing Adenoviral vector)for prostate cancer (2013)
  • Author(s): Kumon H
  • Organizer: Korea-Japan Urological Congress
  • Place of Presentation: Seoul Korea
  • Year and Date: 2013-09-13
• [Presentation] 前立腺がん遺伝子治療 : Ad-REICによるがんワクチン治療法の開発 (2013)
  • Author(s): 公文裕巳
  • Organizer: 浜松カンファランス
  • Place of Presentation: 浜松
  • Year and Date: 2013-08-03
• [Presentation] A super geneexpression system strongly enhances the anticancer effects of the REIC/Dkk-3 encoding adenoviral vector (2013)
  • Author(s): Watanabe M, et al
  • Organizer: Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Japan Okayama
  • Year and Date: 2013-07-05
• [Presentation] Analysis of combination therapy of the adenovirus vector carrying REIC/Dkk-3(Ad -REIC)and the integrin antagonist cilengitide (2013)
  • Author(s): Simazu Y, et al
  • Organizer: Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Japan Okayama
  • Year and Date: 2013-07-05
• [Presentation] Adenovirus-mediated REIC-Dkk-3 gene therapy induces tumor antigen-specific cytotoxic T-cell activation in mouse cancer models (2013)
  • Author(s): Ariyoshi Y, et al
  • Organizer: Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Japan Okayama
  • Year and Date: 2013-07-05
• [Presentation] がんワクチン機能を有する遺伝子医薬Ad-REICの開発 (2013)
  • Author(s): 公文裕巳
  • Organizer: 癌免疫外科研究会
  • Place of Presentation: 岡山
  • Year and Date: 2013-05-16
• [Presentation] A phase I/II study of reduced expression in immortalized cells(REIC/Dkk-3)gene therapy for prostate cancer : Challenge to establish as a cancer vaccine (2013)
  • Author(s): Ariyoshi Y, et al
  • Organizer: Asian Pacific Prostate Society2013
  • Place of Presentation: Melbourne Australia
  • Year and Date: 2013-04-14
• [Presentation] Clinical development of in situ REIC gene therapy in East Asia (2013)
  • Author(s): Kumon H
  • Organizer: Symposium of the East Asian Gene Therapy Innovative Group
  • Place of Presentation: Japan Okayama
  • Year and Date: 2013-03-30
• [Presentation] Emergence of REIC as a novel key player in the cancer arena (2013)
  • Author(s): Kumon H
  • Organizer: Symposium of the East Asian Gene Therapy Innovative Group
  • Place of Presentation: Japan Okayama
  • Year and Date: 2013-03-30
• [Presentation] REIC/Dkk-3 encoding adenoviral vector(Ad-REIC)as a potentially effective therapeutic agent for bladder cancer (2012)
  • Author(s): Hirata T, et al
  • Organizer: Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Japan kumamoto
  • Year and Date: 2012-06-29
• [Presentation] A phase I/II study of reduced expression in immortalized cells(REIC/Dkk-3)gene therapy for prostate cancer : A summary of neoadjuvant group (2012)
  • Author(s): Sasaki K, et al
  • Organizer: Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Japan kumamoto
  • Year and Date: 2012-06-29
• [Presentation] 癌の遺伝子治療 前立腺癌に対する遺伝子治療-新規治療法の開発をめざした岡山大学の取り組み- (2012)
  • Author(s): 佐々木克己
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-04-22
• [Presentation] In situ REIC/Dkk-3 gene therapy creating a new generation of cancer vaccine (2011)
  • Author(s): Kumon H
  • Organizer: Trend of gene & cell therapy as translational research in USA and JAPAN
  • Place of Presentation: Japan Fukuoka
  • Year and Date: 2011-07-14
• [Patent(Industrial Property Rights)] REIC/Dkk-3タンパク質の部分領域ポリペプチド (2011)
  • Inventor(s): 公文 裕巳, 渡部 昌実, 二見 淳一郎, 藤井 康之, 植木 英雄
  • Industrial Property Rights Holder: 岡山大学, 桃太郎源(株)
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: WO2012002582 A1
  • Filing Date: 2011-07-01
  • Overseas
• [Patent(Industrial Property Rights)] REIC発現アデノウイルスベクター (2011)
  • Inventor(s): 渡部 昌実, 公文 裕巳, 許 南浩, 阪口 政清
  • Industrial Property Rights Holder: 岡山大学, 桃太郎源(株)
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2011-117321
  • Filing Date: 2011-05-25