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

Research Project

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
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (28 results)

All 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (18 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

    • Related Report
      2013 Final Research Report
    • 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

    • Related Report
      2013 Final Research Report
    • 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

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+ hematopoietic cells on stromal cells2012

    • Author(s)
      Suzuki K, et al
    • Journal Title

      Int J Oncol

      Volume: 40 Pages: 53-62

    • DOI

      10.3892/ijo.2011.1192

    • Related Report
      2011 Research-status Report
    • 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

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow stromal cell line promotes the proliferation of mast cell progenitors derived from cord blood CD34+ cells under serum-free conditions with a combination of both cell-cell interaction and soluble factors.2011

    • Author(s)
      Fujihara M, Azuma H, Ikeda H, Yamaguchi M, Hamada H.
    • Journal Title

      Artif Cells Blood Substit Immobil Biotechnol

      Volume: Apr;39(2) Issue: 2 Pages: 51-58

    • DOI

      10.3109/10731199.2010.501754

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] EpCAM- and EGFR-targeted selective gene therapy for biliary cancers using Z33-fiber-modified adenovirus2011

    • Author(s)
      Kawashima R, Abei M, Fukuda K, Nakamura K, Murata T, Wakayama M, Seo E, Hasegawa N, Mizuguchi H, Obata Y, Hyodo I, Hamada H, Yokoyama KK.
    • Journal Title

      INTERNATIONAL JOURNAL OF CANCER

      Volume: Sep;129(5) Issue: 5 Pages: 1244-1253

    • DOI

      10.1002/ijc.25758

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] E1A, E1B double-restricted adenovirus enhances the cytotoxicity and antitumor activity of gemcitabine to renal cell carcinoma.2011

    • Author(s)
      Wang H, Satoh M, Chen GP, Li DC, Hamada H, Arai Y.
    • Journal Title

      CHINESE MEDICAL JOURNAL

      Volume: APR;124(7) Pages: 1082-1087

    • Related Report
      2011 Research-status Report
    • 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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] Generation of immunotoxins with super-targeting mAb in acute myeloid leukemia2013

    • Author(s)
      Miki Yamaguchi1, Yukari Nishii1, Hirofumi Hamada1,2
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Generation of Immunotoxins against AML: Cytocidal activities with anti-CD71 mAb2013

    • Author(s)
      Yukari Nishii1, Miki Yamaguchi1, Hirofumi Hamada1,2
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Generation of immunotoxins with super-targeting mAb in the leukemia/lymphoma2013

    • Author(s)
      Yukari Nishii1, Miki Yamaguchi1, Hiroaki Uchida2, Hirofumi Hamada1,2
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Application of in-house monoclonal antibody resources to a fully retargeted oncolytic herpes simplex virus platform2013

    • Author(s)
      Yu Okubo1, Takuma Suzuki1, Tomoko Shibata1, Mao Komai1, Takeshi Fukuhara1, Miki Yamaguchi2, Sachie Hirai2, Yoshitaka Miyagawa3, Justus B. Cohen3, Joseph C. Glorioso3, Hirofumi Hamada1, and Hiroaki Uchida1
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Development of fully retargeted oncolytic herpes simplex virus vectors by insertion of tumor-specific single-chain antibodies into viral envelope glycoprotein D2013

    • Author(s)
      Takuma Suzuki1, Tomoko Shibata1, Yu Okubo1, Takeshi Fukuhara1, Yoshitaka Miyagawa2, Justus B. Cohen2, Joseph C. Glorioso2, Kenji Nakano3, Izumi Kumagai4, Masahide Kuroki5, Miki Yamaguchi6, Sachie Hirai6, Hirofumi Hamada1, and Hiroaki Uchida1
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Application of monoclonal antibody resources to a fully retargeted HSV platform2013

    • Author(s)
      Tomoko Shibata1, Takuma Suzuki1, Yu Okubo1, Mao Komai1, Takeshi Fukuhara1, Miki Yamaguchi2, Sachie Hirai2, Yoshitaka Miyagawa3, Justus B. Cohen3, Joseph C. Glorioso3, Hirofumi Hamada1, and Hiroaki Uchida1
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Establishment of highly functional monoclonal antibodies through novel screening methods for targeted cancer therapy2013

    • Author(s)
      Moegi Sato1, Miki Yamaguchi2, Hitomi Ikeda1, Yuta Matsuura1, Takeshi Fukuhara1, Hirofumi Hamada1, and Hiroaki Uchida1
    • Organizer
      第81回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] Systematic screening of novel monoclonal antibodies targeting human melanoma cells2012

    • Author(s)
      Hirai S, Yamaguchi M, Hamada H
    • Organizer
      The 71st Annual Meeting of Japanese Cancer Association
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Generation of immunotoxins with super-targeting mAb: superior antitumor activities with anti-CD71 mAb agenst AML2012

    • Author(s)
      Nishii Y, Yamaguchi M, Hirai S, Hamada H
    • Organizer
      The 71st Annual Meeting of Japanese Cancer Association
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] Generation of immunotoxins with super-targeting mAb: superior antitumor activities with anti-TROP2 mAb against NSCLC

    • Author(s)
      山口美樹、西井ゆかり、平井幸恵、加藤和則、濱田洋文
    • Organizer
      第15回日本がん免疫学会総会
    • Place of Presentation
      大阪府
    • Related Report
      2011 Research-status Report
  • [Presentation] Generation of immunotoxins with super-targeting monoclonal antibodies (mAb): superior antitumor activities with anti-CD59 mAb against non-small cell lung cancers (NSCLC).

    • 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
      愛知県名古屋市
    • Related Report
      2011 Research-status Report
  • [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

    • 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
      愛知県名古屋市
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research Report
  • [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
    • Filing Date
      2011-06-09
    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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