Development of antibody-drug conjugate to diagnose and treat vulnerable plaque

• Project/Area Number: 15H04821
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kagawa University (2016-2017); Osaka University (2015)
• Principal Investigator: MINAMINO TETSUO 香川大学, 医学部, 教授 (30379234)
• Co-Investigator(Kenkyū-buntansha): 浅井 知浩 静岡県立大学, 薬学部, 准教授 (00381731) ; 松崎 高志 香川大学, 医学部, 研究員 (90456939) ; 村上 和司 香川大学, 医学部附属病院, 講師 (60575207) ; 野間 貴久 香川大学, 医学部附属病院, 准教授 (20363202) ; 富 海英 大阪大学, 医学系研究科, 特任助教(常勤) (70754646) ; 羽尾 裕之 日本大学, 医学部, 教授 (40393243)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: HB-EGF抗体 / HB-EGF抗体結合ベクター / 薬物送達 / 不安定プラーク / 循環器・高血圧 / HB-EGF / バイオテクノロジー

Outline of Final Research Achievements

We have developed the new antibody against HB-EGF (anti-HB-EGF Ab) that can be internalized into the cell after binding. In atherosclerotic lesions, especially vulnerable plaque, the expression of HB-EGF markedly increased. When we administered anti-HB-EGF labeled with siRNA into severe atherosclerosis mouse model, we find that anti-HB-EGF labeled with siRNA efficiently reduced the expression of target molecules with reduced severity of atherosclerosis. Anti-HB-EGF Ab is a promising tool for the diagnosis and therapy for vulnerable plaque.

Research Products

• [Journal Article] Systemic administration of siRNA with anti-HB-EGF antibody-modified lipid nanoparticles for the treatment of triple-negative breast cancer. (2018)
  • Author(s): Okamoto A, Asai T, Hirai Y, Shimizu K, Koide H, Minamino T, Oku N
  • Journal Title: Mol Pharm. Volume: 15 Issue: 4 Pages: 1495-1504
  • DOI: 10.1021/acs.molpharmaceut.7b01055
  • Peer Reviewed / Open Access
• [Journal Article] Development of a novel one-step production system for injectable liposomes under GMP (2017)
  • Author(s): Araki Ryo、Matsuzaki Takashi、Nakamura Ayumi、Nakatani Daisaku、Sanada Shoji、Fu Hai Ying、Okuda Keiji、Yamato Masaki、Tsuchida Shota、Sakata Yasushi、Minamino Tetsuo
  • Journal Title: Pharm Dev Technol. Volume: 10 Issue: 6 Pages: 1-6
  • DOI: 10.1080/10837450.2017.1290106
  • Peer Reviewed
• [Journal Article] Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats. (2017)
  • Author(s): Okuda K, Fu HY, Matsuzaki T, Araki R, Tsuchida S, Thanikachalam PV, Fukuta T, Asai T, Yamato M, Sanada S, Asanuma H, Asano Y, Asakura M, Hanawa H, Hao H, Oku N, Takashima S, Kitakaze M, Sakata Y, Minamino T.
  • Journal Title: PLoS One. Volume: 11 Issue: 8 Pages: e0160944-e0160944
  • DOI: 10.1371/journal.pone.0160944
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone Deacetylase Inhibitor Phenylbutyrate Exaggerates Heart Failure in Pressure Overloaded Mice independently of HDAC inhibition. (2016)
  • Author(s): Ma J, Luo T, Zeng Z, Fu H, Asano Y, Liao Y, Minamino T, Kitakaze M.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 34036-34036
  • DOI: 10.1038/srep34036
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of the Mtus1 Splice Variant as a Novel Inhibitory Factor Against Cardiac Hypertrophy. (2016)
  • Author(s): Ito S, Asakura M, Liao Y, Min KD, Takahashi A, Shindo K, Yamazaki S, Tsukamoto O, Asanuma H, Mogi M, Horiuchi M, Asano Y, Sanada S, Minamino T, Takashima S, Mochizuki N, Kitakaze M.
  • Journal Title: J Am Heart Assoc. Volume: 5 Issue: 7
  • DOI: 10.1161/jaha.116.003521
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Btg2 is a Negative Regulator of Cardiomyocyte Hypertrophy through a Decrease in Cytosolic RNA. (2016)
  • Author(s): Masumura Y, Higo S, Asano Y, Kato H, Yan Y, Ishino S, Tsukamoto O, Kioka H, Hayashi T, Shintani Y, Yamazaki S, Minamino T, Kitakaze M, Komuro I, Takashima S, Sakata Y.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 28592-28592
  • DOI: 10.1038/srep28592
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin-Induced Cardiac Dysfunction. (2016)
  • Author(s): Fu HY, Sanada S, Matsuzaki T, Liao Y, Okuda K, Yamato M, Tsuchida S, Araki R, Asano Y, Asanuma H, Asakura M, French BA, Sakata Y, Kitakaze M, Minamino T.
  • Journal Title: Circ Res. Volume: 118 Issue: 5 Pages: 798-809
  • DOI: 10.1161/circresaha.115.307604
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An interaction between GLP-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia/reperfusion injury. (2015)
  • Author(s): Ihara M, Asanuma H, Yamazaki S, Kato H, Asano Y, Shinozaki Y, Mori H, Minamino T, Asakura M, Sugimachi M, Mochizuki N, Kitakaze M.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: in press Issue: 10 Pages: 1287-1297
  • DOI: 10.1152/ajpheart.00835.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Late Breaking Clinical Trials 2 (HF) : Low dose Erythropoietin in Patients with ST segment Elevation Myocardial Infarction (EPO AMI II Study): A Randomized Controlled Clinical Trial (2017)
  • Author(s): 南野哲男
  • Organizer: 第81回日本循環器学会学術集会総会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] A chemical ER chaperone attenuates cardiac dysfunction by doxorubicin (2016)
  • Author(s): 南野哲男
  • Organizer: Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: 仙台
  • Year and Date: 2016-05-20
  • Int'l Joint Research / Invited
• [Presentation] シンポジウム３「先端医療とDDSの進展」ドッラクデリバリーシステムを用いた急性心筋梗塞治療薬の開発 (2016)
  • Author(s): 南野哲男
  • Organizer: 第32回日本DDS学会学術集会
  • Place of Presentation: 岐阜
  • Year and Date: 2016-05-19
  • Invited
• [Presentation] A Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin- induced Cardiac Dysfunction (2016)
  • Author(s): 南野哲男
  • Organizer: 日本循環器学会学術集会プレナリーセッション 20年後を見据えた心不全診療のあり方 ―基礎・臨床研究からの提言と臨床での実践―
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18