Development of conditionally replicating adenovirus that treats human ES/iPS-derived tumor

• Project/Area Number: 23659159
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kagoshima University
• Principal Investigator: KOSAI kenichirou 鹿児島大学, 医歯(薬)学総合研究科, 教授 (90258418)
• Co-Investigator(Kenkyū-buntansha): IRIE Rie 鹿児島大学, 大学院・医歯学総合研究科, 助教 (90381178)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 再生医学

Research Abstract

The tumor that is derived from the contaminated undifferentiated-cells is the major obstacle to the clinical application of human ES and/or iPS cell-based regenerative medicine. Here we developed a novel methodology that might conquer this obstacle to some degrees using m-CRA (conditionally replicating adenovirus with multiple tumor-specific factors), which we had initially developed for treating cancer. This methodology is not only a scientifically novel and original but also meaningful in terms of facilitating clinical development of these sorts of innovative therapy.

Research Products

• [Journal Article] Intramuscular injection of adenoviral hepatocyte growth factor at a distal site ameliorates dextran sodium sulfate-induced colitis in mice (2014)
  • Author(s): Yuge K, Takahashi T, Khai NC, Goto K, Fujiwara T, Fujiwara H, Kosai K
  • Journal Title: Int J Mol Med Volume: 33(5) Issue: 5 Pages: 1064-1074
  • DOI: 10.3892/ijmm.2014.1686
  • Peer Reviewed
• [Journal Article] Survivin-responsive conditionally replicating adenovirus kills rhabdomyosarcoma stem cells more efficiently than their progeny (2014)
  • Author(s): Tanoue K, Wang Y, Ikeda M , Mitsui K, Irie R , Setoguchi T, Komiya S, Natsugoe S, Kosai K
  • Journal Title: J Trans Med Volume: 12 Issue: 1 Pages: 27-27
  • DOI: 10.1186/1479-5876-12-27
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical analysis of the acid secretion potency in gastric parietal cells (2013)
  • Author(s): Irie-Maezono R. and Tsuyama S
  • Journal Title: Open journal of Cell biology Volume: 2 Issue: 04 Pages: 179-185
  • DOI: 10.4236/cellbio.2013.24020
  • Peer Reviewed
• [Journal Article] Alterations of Gene Expression and Glutamate Clearance in Astrocytes Derived from an MeCP2-null Mouse Model of Rett Syndrome (2012)
  • Author(s): Okabe Y, Takahashi T, Mitsumasu C, Kosai K, MD, Tanaka E, Matsuishi T
  • Journal Title: PLoS ONE Volume: 7(4) Issue: 4 Pages: e35354-e35354
  • DOI: 10.1371/journal.pone.0035354
  • Peer Reviewed
• [Journal Article] FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure. (2012)
  • Author(s): Hino S, Sakamoto A, Nagaoka K, Anan K, Wang Y, Mimasu S, Umehara T, Yokoyama S, Kosai K, and Nakao M
  • Journal Title: Nat. Commun Volume: 27;3 Issue: 1 Pages: 758-758
  • DOI: 10.1038/ncomms1755
  • Peer Reviewed
• [Journal Article] Targeting CD9 produces stimulus-independent antiangiogenic effects predominantly in activated endothelial cells during angiogenesis : A novel antiangiogenic therapy (2011)
  • Author(s): Kamisasanuki T, Tokushige S, Terasaki H, Khai NC, Wang Y, Sakamoto T, Kosai K
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 413(1) Pages: 128-35
  • Peer Reviewed
• [Journal Article] Assessment of an altered E1B promoter on the specificity and potency of triple-regulated conditionally replicating adenoviruses (CRA)⎯Implications for the generation of ideal m-CRAs (2011)
  • Author(s): Horikawa Y, Wang Y, Nagano S, Kamizono J, Ikeda M, Komiya S, Kosai K
  • Journal Title: Cancer Gene Ther Volume: 18(10) Pages: 724-33
  • Peer Reviewed
• [Journal Article] Recombinant soluble form of HB-EGF protein therapy drastically inhibits Fas-mediated fulminant hepatic failure : Implications in clinical application (2011)
  • Author(s): Khai NC, Sakamoto K, Takamatsu H, Matsufuji H, Kosai K
  • Journal Title: Hepatol Res Volume: 41(6) Pages: 594-596
  • Peer Reviewed
• [Journal Article] Therapeutic effects of vitamin A on experimental cholestatic rats with hepatic fibrosis (2011)
  • Author(s): Murakami KI, Kaji T, Shimono R, Hyashida Y, Matsufuji H, Tsuyama S, Maezono R, Kosai K, Takamatsu H
  • Journal Title: Pediatr Surg Int Volume: 27(8) Pages: 863-70
  • Peer Reviewed
• [Journal Article] Targeting CD9 produces stimulus-independent antiangiogenic effects predominantly in activated endothelial cells during angiogenesis: A novel antiangiogenic therapy. (2011)
  • Author(s): Kamisasanuki T, Wang Y, Tokushige S, Terasaki H, Khai NC, Wang Y, Sakamoto T, Kosai K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 16 Pages: 128-135
  • Peer Reviewed
• [Journal Article] Assessment of an altered E1B promoter on the specificity and potency of triple-regulated conditionally replicating adenoviruses (CRA) ⎯Implications for the generation of ideal m-CRAs (2011)
  • Author(s): Horikawa Y, Wang Y, Nagano S, Kamizono J, Ikeda M, Komiya S, Kosai K.
  • Journal Title: Cancer Gene Ther. Volume: 18 Pages: 724-733
  • Peer Reviewed
• [Journal Article] Recombinant soluble form of HB-EGF protein therapy drastically inhibits Fas-mediated fulminant hepatic failure: Implications in clinical application. (2011)
  • Author(s): Khai NC, Sakamoto K, Takamatsu H, Matsufuji H, Kosai K.
  • Journal Title: Hepatol Res. Volume: 41 Pages: 594-596
  • Peer Reviewed
• [Journal Article] Therapeutic effects of vitamin A on experimental cholestatic rats with hepatic fibrosis. (2011)
  • Author(s): Murakami KI, Kaji T, Shimono R, Hyashida Y, Matsufuji H, Tsuyama S, Maezono R, Kosai K, Takamatsu H.
  • Journal Title: Pediatr Surg Int. Volume: 27 Pages: 863-870
  • Peer Reviewed
• [Presentation] 新しい遺伝子治療ウイルスベクターの開発と基礎・臨床への応用 (2014)
  • Author(s): 小戝健一郎
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島(国内・ランチョンセミナー)
  • Year and Date: 2014-03-16
• [Presentation] 多能性幹細胞の再生医療応用における新規腫瘍化阻止技術の開発(1)ヒトES 細胞での検証 (2014)
  • Author(s): 井手佳菜子, 三井薫, 小戝健一郎
  • Organizer: 第7回桜ヶ丘地区基礎系研究発表会
  • Place of Presentation: 鹿児島(国内・口頭発表)
  • Year and Date: 2014-01-16
• [Presentation] 多能性幹細胞の再生医療応用における新規腫瘍化阻止技術の開発(2)マウスES 細胞での検証 (2014)
  • Author(s): 松下洋平, 井手佳菜子, 三井薫, 小戝健一郎
  • Organizer: 第7回桜ヶ丘地区基礎系研究発表会
  • Place of Presentation: 鹿児島(国内・口頭発表)
  • Year and Date: 2014-01-16
• [Presentation] アデノウイルスベクターでのヒト多能性幹細胞への効率的遺伝子導入技術の開発 (2014)
  • Author(s): 三井薫, 高橋知之, 井手佳菜子, 小戝健一郎
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都(国内・ポスター)
• [Presentation] 新しい遺伝子治療ウイルスベクターの開発と基礎・臨床への応用 (2014)
  • Author(s): 小戝健一郎
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
• [Presentation] アデノウイルスベクターでのヒト多能性幹細胞への効率的遺伝子導入技術の開発 (2014)
  • Author(s): 三井薫、高橋知之、井手佳菜子、小戝健一郎
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都
• [Presentation] 多能性幹細胞の再生医療応用における新規腫瘍化阻止技術の開発(1)ヒトES細胞での検証 (2014)
  • Author(s): 井手佳菜子、三井薫、小戝健一郎
  • Organizer: 第7回桜ヶ丘地区基礎系研究発表会
  • Place of Presentation: 鹿児島
• [Presentation] 多能性幹細胞の再生医療応用における新規腫瘍化阻止技術の開発(2)マウスES細胞での検証 (2014)
  • Author(s): 松下洋平、井手佳菜子、三井薫、小戝健一郎
  • Organizer: 第7回桜ヶ丘地区基礎系研究発表会
  • Place of Presentation: 鹿児島
• [Presentation] 癌を標的治療する増殖型アデノウイルスの独自技術開発と臨床応用への展望 (2013)
  • Author(s): 小戝健一郎
  • Organizer: 鹿児島がんフォーラム
  • Place of Presentation: 鹿児島
  • Year and Date: 2013-11-30
• [Presentation] 革新的ながん治療薬(癌だけを殺すウイルス)の開発と臨床応用に向けて (2013)
  • Author(s): 小戝健一郎
  • Organizer: 鹿児島大学公開講座
  • Place of Presentation: 鹿児島
  • Year and Date: 2013-07-27
• [Presentation] 増殖型アデノウイルスベクターを用いた安全なヒトES/iPS細胞治療の開発 (2013)
  • Author(s): 井手佳菜子, 三井薫, 小戝健一郎
  • Organizer: 第6回桜ヶ丘地区基礎系研究発表会
  • Place of Presentation: 鹿児島(国内・口頭発表)
  • Year and Date: 2013-01-24
• [Presentation] Immunohistochemical comparative analysis of the sphere cells of CD133-positive pancreatic cancer cells with iPS cells. CD133+膵がんSphere 形成細胞とiPS 細胞の免疫組織学的比較解析 (2013)
  • Author(s): 宮崎優美, 王宇清, 三井薫, 丁強, 政幸一郎, 松原修一郎, 小戝健一郎, 高尾尊身
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 増殖型アデノウイルスベクターを用いた安全なヒトES/iPS 細胞治療の開発 (2013)
  • Author(s): 井手佳菜子、三井薫、小戝健一郎
  • Organizer: 第6回桜ヶ丘地区基礎系研究発表会
  • Place of Presentation: 鹿児島
• [Presentation] 再生医療と癌の遺伝子治療-技術と臨床応用の現状と展望- (2012)
  • Author(s): 小戝健一郎
  • Organizer: 平成24年度鹿児島大学医学部産科学婦人科学教室碩門会
  • Place of Presentation: 鹿児島(国内・特別講演)
  • Year and Date: 2012-12-01
• [Presentation] Efficient treatment of Rhabdomyosarcoma-initiating cells by Survivin-responsive conditionally replicating adenovirus : Promising m-CRA strategy for treating cancer stem cells (2012)
  • Author(s): Tanoue K, Wang Y, Ikeda M, Mitsui K, Setoguchi T, Komiya S, Natsugoe S, Kosai K
  • Organizer: The American Society of Gene Therapy's 15h Annual Meeting
  • Place of Presentation: Philadelphia, USA(国際・ポスター)
• [Presentation] Development of conditionally replicating adenovirus specifically targeting and/or efficiently treating cancer stem cells (2012)
  • Author(s): Ken-ichiro Kosai
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌(国内, 口演[English])
• [Presentation] Survivin-Responsive Conditionally Replicating Adenovirus Efficiently Treats Rhabdomyosarcoma-Initiating Cells (2012)
  • Author(s): Kiyonori Tanoue, Yuqing Wang, Takao Setoguchi, Setsuro Komiya, Shoji Natusgoe, Ken-ichiro Kosai
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌(国内, 口演[Japanese])
• [Presentation] ヒトES/iPS 細胞での再生医療の課題を克服する独自のアデノウイルスベクターと発現技術の開発 (2012)
  • Author(s): 小戝健一郎, 三井薫, 王宇清, 高橋知之
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: 横浜(国内・パネルディスカッション)
• [Presentation] 独自開発の増殖型アデノウイルスベクターで癌幹細胞は効果的に治療できる (2012)
  • Author(s): 田上聖徳, 王宇清, 池田美奈子, 三井薫, 瀬戸口啓夫, 小宮節郎, 夏越祥次, 小戝健一郎
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: 横浜(国内・ポスター)
• [Presentation] 増殖型アデノウイルスベクターを用いた安全なヒトES/iPS 細胞治療の開発 (2012)
  • Author(s): 三井薫, 井手佳菜子, 高山明子, 小戝健一郎
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: 横浜(国内・口演)
• [Presentation] 癌の遺伝子異常を標的とした診断と治療の可能性 (2012)
  • Author(s): 小戝健一郎
  • Organizer: 第175回日本医学放射線学会九州地方会
  • Place of Presentation: 鹿児島(国内・特別講演)
• [Presentation] 再生医療と癌の遺伝子治療－技術と臨床応用の現状と展望 (2012)
  • Author(s): 小戝健一郎
  • Organizer: 平成24年度鹿児島大学医学部産科学婦人科学教室碩門会
  • Place of Presentation: 鹿児島
• [Presentation] Development of conditionally replicating adenovirus specifically targeting and/or efficiently treating cancer stem cells (2012)
  • Author(s): Ken-ichiro Kosai
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Survivin-Responsive Conditionally Replicating Adenovirus Efficiently Treats Rhabdomyosarcoma-Initiating Cells (2012)
  • Author(s): Kiyonori Tanoue, Yuqing Wang, Takao Setoguchi, Setsuro Komiya, Shoji Natusgoe, Ken-ichiro Kosai.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] ヒトES/iPS細胞での再生医療の課題を克服する独自のアデノウイルスベクターと発現技術の開発 (2012)
  • Author(s): 小戝健一郎、三井薫、王宇清、高橋知之
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: 横浜
• [Presentation] 独自開発の増殖型アデノウイルスベクターで癌幹細胞は効果的に治療できる (2012)
  • Author(s): 田上聖徳、王宇清、池田美奈子、三井薫、瀬戸口啓夫、小宮節郎、夏越祥次、小戝健一郎
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: 横浜
• [Presentation] 増殖型アデノウイルスベクターを用いた安全なヒトES/iPS細胞治療の開発 (2012)
  • Author(s): 三井薫、井手佳菜子、高山明子、小戝健一郎
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: 横浜
• [Presentation] 癌の遺伝子異常を標的とした診断と治療の可能性 (2012)
  • Author(s): 小戝 健一郎
  • Organizer: 第175回日本医学放射線学会九州地方会
  • Place of Presentation: 鹿児島
• [Presentation] Efficient treatment of Rhabdomyosarcoma-initiating cells by Survivin-responsive conditionally replicating adenovirus : Promising m-CRA strategy for treating cancer stem cells (2012)
  • Author(s): Tanoue K, Wang Y, Ikeda M, Mitsui K, Setoguchi T, Komiya S, Natsugoe S, Kosai K
  • Organizer: The American Society of Gene Therapy’s 15h Annual Meeting
  • Place of Presentation: Philadelphia, USA)
• [Presentation] HB-EGF/HGF Hepatic Gene Therapy Effectively Inhibits Bile Duct Ligated Cholestatic Liver Injury In Mice In Their Different Therapeutic Modes (2011)
  • Author(s): Kosai K, Sakamoto K, Khai NC, Wang Y, Maezono R, Tanoue K, Hideo T, Matsufuji H
  • Organizer: The American Society of Gene Therapy's 14h Annual Meeting
  • Place of Presentation: Seattle, USA
• [Presentation] HB-EGF/HGF HEPATIC GENE THERAPY FOR BILE DUCT LIGATED CHOLESTATIC LIVER INJURY IN MICE : THEIR DIFFERENT AND/OR SYNERGIC THERAPEUTIC EFFECTS (2011)
  • Author(s): Sakamoto K, Khai NC, Wang Y, Maezono R, Tanoue K, Matsufuji H, Hideo T, Kosai K
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡(国内・口演)
• [Presentation] ASSESSMENT OF AN ALTERED E1B PROMOTER ON THE SPECIFICITY AND POTENCY OF TRIPLE-REGULATED CONDITIONALLY REPLICATING ADENOVIRUSES (CRA) : A NEW INSIGHT TO GENERATE IDEAL m-CRAS (2011)
  • Author(s): Kosai K, Horikawa Y, Wang Y, Nagano S, Kamizono J, Ikeda M, Komiya S
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡(国内・口演)
• [Presentation] HB-EGF/HGF HEPATIC GENE THERAPY FOR BILE DUCT LIGATED CHOLESTATIC LIVER INJURY IN MICE: THEIR DIFFERENT AND/OR SYNERGIC THERAPEUTIC EFFECTS.
  • Author(s): Sakamoto K, Khai NC, Wang Y, Maezono R, Tanoue K, Matsufuji H, Hideo T, Kosai K.
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
• [Presentation] ASSESSMENT OF AN ALTERED E1B PROMOTER ON THE SPECIFICITY AND POTENCY OF TRIPLE-REGULATED CONDITIONALLY REPLICATING ADENOVIRUSES (CRA): A NEW INSIGHT TO GENERATE IDEAL m-CRAS.
  • Author(s): Kosai K, Horikawa Y, Wang Y, Nagano S, Kamizono J, Ikeda M, Komiya S.
  • Organizer: 第17回日本遺伝子治療学会
  • Place of Presentation: 福岡
• [Presentation] HB-EGF/HGF Hepatic Gene Therapy Effectively Inhibits Bile Duct Ligated Cholestatic Liver Injury In Mice In Their Different Therapeutic Modes.
  • Author(s): Kosai K, Sakamoto K, Khai NC, Wang Y, Maezono R, Tanoue K, Hideo T, Matsufuji H.
  • Organizer: 第14回米国遺伝子治療学会
  • Place of Presentation: シアトル
• [Remarks]
  • URL: http://www.kufm.kagoshima-u.ac.jp/~anatomy2/
• [Patent(Industrial Property Rights)] 幹細胞における腫瘍化原因細胞の新たな標識法と治療法 (2014)
  • Inventor(s): 小戝健一郎、三井薫、井手佳菜子
  • Industrial Property Rights Holder: 鹿児島大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-004262
  • Filing Date: 2014-01-14
• [Patent(Industrial Property Rights)] 癌幹細胞を標的とするウイルスベクター (2013)
  • Inventor(s): 小戝健一郎、王宇清
  • Industrial Property Rights Holder: 鹿児島大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-09-24
  • Overseas
• [Patent(Industrial Property Rights)] Auroraキナーゼプロモーターを含む増殖制御型ウイルスベクター (2013)
  • Inventor(s): 小戝 健一郎
  • Industrial Property Rights Holder: 鹿児島大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-07-05
  • Overseas
• [Patent(Industrial Property Rights)] シノビオリンプロモーターを含む増殖制御型ウイルスベクター (2012)
  • Inventor(s): 小戝健一郎
  • Industrial Property Rights Holder: 小戝健一郎
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-184651
  • Filing Date: 2012-08-23
• [Patent(Industrial Property Rights)] ヒトES/iPS細胞における遺伝子発現方法 (2012)
  • Inventor(s): 小戝健一郎、三井薫、高橋知之
  • Industrial Property Rights Holder: 小戝健一郎、三井薫、高橋知之
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-117128
  • Filing Date: 2012-05-23
• [Patent(Industrial Property Rights)] Auroraキナーゼプロモーターを含む増殖制御型ウイルスベクター (2011)
  • Inventor(s): 小戝 健一郎
  • Industrial Property Rights Holder: 鹿児島大学
  • Filing Date: 2011
  • Overseas