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2013 Fiscal Year Final Research Report

Generation of immunotoxins with super-targeting mAb in the acute myelocytic leukemia

Research Project

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Project/Area Number 23501309
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Clinical oncology
Research InstitutionSapporo Medical University

Principal Investigator

YAMAGUCHI MIKI  札幌医科大学, 医学部, 助教 (10530454)

Co-Investigator(Kenkyū-buntansha) HAMADA Hirofumi  東京薬科大学, 生命科学部, 教授 (00189614)
HIRAI Sachie  札幌医科大学, 医学部, 助手 (20218754)
UCHIDA Hiroaki  東京薬科大学, 生命科学部, 准教授 (20401250)
Project Period (FY) 2011 – 2013
KeywordsAML / 標的治療 / イミュノトキシン / モノクローナル抗体 / DT3C / ADC
Research Abstract

We generated a recombinant fusion protein DT3C, which contained the catalytic and translocation domain of the truncated diphtheria toxin (DT) as well as the three IgG-binding C domains of streptococcal protein G (3C). Fc of MoAb binds with DT3C, resulting in a MoAb-DT3C complex (two DT3C molecules conjugated with one IgG molecule). The MoAb-DT3C complex binds with the surface Ag, being followed by internalization and translocation into the cytoplasm, leads to the cytocydal effect by protein synthesis inhibition of DT. By using these, we developed a unique screening system to establish cancer-targetable antigens/antibodies sets. In total 224 MoAb clones were obtained which performed immunotoxin cytocydal on leukemic cells. Our method provide an excellent way to obtain promising superior mAbs for antibodies drug conjugation(ADC) therapy.

  • Research Products

    (12 results)

All 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (6 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Expression of HSV-1 receptors in EBV-associated lymphoproliferative disease determines susceptibility to oncolytic HSV2013

    • Author(s)
      Wang PY, Currier MA, Hansford L, Kaplan D, Chiocca EA, Uchida H, Goins WF, Cohen JB, Glorioso JC, van Kuppevelt TH, Mo X, Cripe TP
    • Journal Title

      Gene Ther

      Volume: 20(7) Pages: 761-769

    • Peer Reviewed
  • [Journal Article] Effective treatment of an orthotopic xenograft model of human glioblastoma using an EGFR-retargeted oncolytic herpes simplex virus2013

    • Author(s)
      Uchida H, Marzulli M, Nakano K, Goins WF, Chan J, Hong CH, Mazzacurati L, Yoo JY, Haseley A, Nakashima H, Baek H, Kwon H, Kumagai I, Kuroki M, Kaur B, Chiocca EA, Grandi P, Cohen JB, Glorioso JC
    • Journal Title

      Mol Ther

      Volume: 21(3) Pages: 561-569

    • Peer Reviewed
  • [Journal Article] Novel mutations in gB and gH circumvent the requirement for known gD receptors in HSV-1 entry and cell-to-cell spread2013

    • Author(s)
      Uchida H, Chan J, Shrivastava I, Reinhart B, Grandi P, Glorioso JC, Cohen JB
    • Journal Title

      J Virol

      Volume: 87(3) Pages: 1430-1442

    • Peer Reviewed
  • [Journal Article] Epigenetic modulation enhances the therapeutic effect of anti-IL-13R(alpha)2 antibody in human mesothelioma xenografts2011

    • Author(s)
      Takenouchi M, Hirai S, Sakuragi N, Yagita H, Hamada H, Kato K
    • Journal Title

      Clin Cancer Res

      Volume: 17(9) Pages: 2819-2829

    • Peer Reviewed
  • [Presentation] 急性骨髄性白血病に対するスーパー標的化抗体を用いたイミュノトキシンの開発2013

    • Author(s)
      山口美樹、西井ゆかり、濱田洋文
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2013-10-12
  • [Presentation] 白血病/リンパ腫に対するスーパー標的化抗体を用いたイムノトキシンの開発2013

    • Author(s)
      西井ゆかり、山口美樹、平井幸恵、内田宏昭、濱田洋
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-03
  • [Presentation] スーパー標的化抗体を用いたimmunotoxin の開発:AML に対する抗CD71 抗体を用いた抗腫瘍活性2012

    • Author(s)
      西井ゆかり、山口美樹、平井幸恵、濱田洋文
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-20
  • [Presentation] メラノーマ標的化新規モノクローナル抗体の網羅的解析2012

    • Author(s)
      平井幸恵、山口美樹、濱田洋文
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-19
  • [Presentation] メラノーマに対する新規標的化抗体の樹立と機能解析2011

    • Author(s)
      平井幸恵、山口美樹、濱田洋文
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-05
  • [Presentation] スーパー標的化抗体を用いたImmunotoxin の開発:非小細胞肺癌に対するCD59 抗体を用いた抗腫瘍活性2011

    • Author(s)
      山口美樹、西井ゆかり、平井幸恵、濱田洋文
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-05
  • [Remarks]

    • URL

      http://web.sapmed.ac.jp/molm/

  • [Patent(Industrial Property Rights)] 抗Trop-2 抗体2011

    • Inventor(s)
      山口美樹、加藤和則、濱田洋文、他
    • Industrial Property Rights Holder
      札幌医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      PCT/2011/063294, US20120237518
    • Filing Date
      2011-06-09

URL: 

Published: 2015-07-16  

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