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Development of tumor-targeted therapy using lentivirus-displayed antibody library

Research Project

Project/Area Number 24650629
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Tumor immunology
Research InstitutionTottori University

Principal Investigator

NAKAMURA Takafumi  鳥取大学, 医学(系)研究科(研究院), 准教授 (70432911)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords癌 / 抗体 / バイオテクノロジー / ウイルス / 生体機能利用
Research Abstract

We previously showed that antibody-targeted cell fusion can be achieved by engineering a fusogenic viral membrane glycoprotein complex. Single-chain antibodies were displayed at the extracellular C terminus of the measles hemagglutinin (H) protein, and combinations of point mutations were introduced to ablate its ability to trigger fusion through the native viral receptors CD46 and SLAM. When coexpressed with the measles fusion (F) protein, the retargeted H proteins (Haals-scFvs) could mediate antibody-targeted cell fusion of receptor-negative or receptor-positive index cells with receptor-positive target cells. Now we have successfully pseudotyped lentiviral vectors with the glycoproteins Haals-scFv and F for targeted cell entry. Thus, the use of single chain antibodies for targeting potentially allows us to redirect the virus against any chosen cellular receptor. We also try to develop lentivirus-displayed scFvs library using the technology for identification of tumor-specific scFv.

Report

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

    (29 results)

All 2014 2013 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (16 results) Book (2 results) Remarks (7 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Antibody neutralization of retargeted measles viruses2014

    • Author(s)
      Lech PJ, Pappoe R, Nakamura T, Russell SJ
    • Journal Title

      Virology

      Volume: 454-455 Pages: 237-246

    • DOI

      10.1016/j.virol.2014.01.027

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Combined Cytolytic Effects of a Vaccinia Virus Encoding a Single Chain Trimer of MHC-I with a Tax-Epitope and Tax-Specific CTLs on HTLV-I-Infected Cells in a Rat Model2014

    • Author(s)
      Ohashi T, Nakamura T, Kidokoro M, Zhang X, Shida H
    • Journal Title

      BioMed Research International.

      Volume: 2014 Pages: 902478-902478

    • DOI

      10.1155/2014/902478

    • NAID

      120005434503

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coxsackievirus B3 Is an Oncolytic Virus with Immunostimulatory Properties that Is Active Against Lung Adenocarcinoma2012

    • Author(s)
      Miyamoto S, Inoue H, Nakamura T, Yamada M, Sakamoto C, Urata Y, Okazaki T, Marumoto T, Takahashi A, Takayama K, Nakanishi Y, Shimizu H, Tani K
    • Journal Title

      Cancer Research

      Volume: (掲載確定)(印刷中) Issue: 10 Pages: 2609-2621

    • DOI

      10.1158/0008-5472.can-11-3185

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Safety profile, tumor selectivity and oncolytic effects after systemic administration of oncolytic vaccinia virus MDVV2013

    • Author(s)
      Takafumi Nakamura
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜(Oral presentation)
    • Year and Date
      2013-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] SYSTEMIC CANCER VIROTHERAPY WITH MDVV, A COMBINED miRNA-REGULATED AND THYMIDINE KINASE-DELETED ONCOLYTIC VACCINIA VIRUS2013

    • Author(s)
      Naoyoshi Nitta, Nao Okada, Ikumi Goto, Masato Yamane, Motomu Nakatake, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      The 19th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      岡山(Oral presentation)
    • Year and Date
      2013-07-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Systemic cancer virotherapy with MDVV, a combined miRNA-regulated and thymidine kinase-deleted oncolytic vaccinia virus2013

    • Author(s)
      Naoyoshi Nitta, Nao Okada, Ikumi Goto, Motomu Nakatake, Masato Yamane, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      The Seventh International Meeting On Replicating Oncolytic Virus Therapeutics
    • Place of Presentation
      Quebec City, Canada(Poster presentation)
    • Year and Date
      2013-06-16
    • Related Report
      2013 Final Research Report
  • [Presentation] MicroRNA regulation of viral replication for oncolytic virothrapy2013

    • Author(s)
      Takafumi Nakamura
    • Organizer
      The 2nd Meeting on RNA and Biofunctions-ASIA Study"RNA Biofunctions and Viruses
    • Place of Presentation
      福岡(Oral presentation)
    • Year and Date
      2013-01-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Systemic cancer retargeted measles viruses. Virology therapy with MDVV, a combined 454-455 : 237-246, 2014. doi : miRNA-regulated and thymidine kinase-deleted oncolytic vaccinia virus2012

    • Author(s)
      Takafumi Nakamura
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌(Oral presentation)
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
  • [Presentation] マイクロRNAによって制御されるウイルスベクターの開発2012

    • Author(s)
      中村貴史
    • Organizer
      第14回日本RNA学会年会
    • Place of Presentation
      仙台(Oral presentation)
    • Year and Date
      2012-07-18
    • Related Report
      2013 Final Research Report
  • [Presentation] SYSTEMIC ONCOLYTIC VIROTHERAPY WITH TUMOR-SPECIFIC REPLICATING VACINIA VIRUSES2012

    • Author(s)
      Mina Hikichi, Minoru Kidokoro, Hisatoshi Shida, Hideaki Tahara, Takafumi Nakamura
    • Organizer
      The 18th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      熊本(Oral presentation)
    • Year and Date
      2012-06-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Systemic cancer virotherapy with MDVV, a combined miRNA-regulated and thymidine kinase-deleted oncolytic vaccinia virus2012

    • Author(s)
      Mina Hikichi, Takafumi Nakamura
    • Organizer
      The 15th Annual Meeting of American Society of Gene & Cell Therapy
    • Place of Presentation
      Philadelphia, USA(Poster presentation)
    • Year and Date
      2012-05-17
    • Related Report
      2013 Final Research Report
  • [Presentation] Safety profile, tumor selectivity and oncolytic effects after systemic administration of oncolytic vaccinia virus MDVV

    • Author(s)
      Naoyoshi Nitta, Nao Okada, Ikumi Goto, Masato Yamane, Motomu Nakatake, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] SYSTEMIC CANCER VIROTHERAPY WITH MDVV, A COMBINED miRNA-REGULATED AND THYMIDINE KINASE-DELETED ONCOLYTIC VACCINIA VIRUS

    • Author(s)
      Naoyoshi Nitta, Nao Okada, Ikumi Goto, Masato Yamane, Motomu Nakatake, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      The 19th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      岡山(岡山コンベンションセンター)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Systemic cancer virotherapy with MDVV, a combined miRNA-regulated and thymidine kinase-deleted oncolytic vaccinia virus

    • Author(s)
      Naoyoshi Nitta, Nao Okada, Ikumi Goto, Motomu Nakatake, Masato Yamane, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      The Seventh International Meeting On Replicating Oncolytic Virus Therapeutics
    • Place of Presentation
      Quebec City, Canada(Chateau Frontenac )
    • Related Report
      2013 Annual Research Report
  • [Presentation] MicroRNA regulation of viral replication for oncolytic virothrapy

    • Author(s)
      Nakamura T
    • Organizer
      The 2nd Meeting on RNA and Biofunctions-ASIA Study “RNA Biofunctions and Viruses”
    • Place of Presentation
      ホテルレオパレス博多(福岡)
    • Related Report
      2012 Research-status Report
  • [Presentation] Systemic cancer therapy with MDVV, a combined miRNA-regulated and thymidine kinase-deleted oncolytic vaccinia virus

    • Author(s)
      Nakamura T
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Related Report
      2012 Research-status Report
  • [Presentation] マイクロRNAによって制御されるウイルスベクターの開発

    • Author(s)
      中村貴史
    • Organizer
      第14回日本RNA学会年会
    • Place of Presentation
      北大学百周年記念会館(仙台)
    • Related Report
      2012 Research-status Report
  • [Presentation] SYSTEMIC ONCOLYTIC VIROTHERAPY WITH TUMOR-SPECIFIC REPLICATING VACINIA VIRUSES

    • Author(s)
      Nakamura T
    • Organizer
      The 18th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      ホテル熊本テルサ(熊本)
    • Related Report
      2012 Research-status Report
  • [Presentation] Systemic cancer virotherapy with MDVV, a combined miRNA-regulated and thymidine kinase-deleted oncolytic vaccinia virus

    • Author(s)
      Nakamura T
    • Organizer
      The 15th Annual Meeting of American Society of Gene & Cell Therapy
    • Place of Presentation
      Pennsylvania Convention Center (Philadelphia, USA)
    • Related Report
      2012 Research-status Report
  • [Book] miRNA制御ウイルスによるがん細胞特異的治療法の開発.遺伝子医学MOOK23号2012

    • Author(s)
      中村貴史
    • Publisher
      落谷孝広監修、株式会社メディカルドゥ
    • Related Report
      2013 Final Research Report
  • [Book] 臨床・創薬利用が見えてきたmiRcroRNA 「miRNA制御ウイルスによるがん細胞特異的治療法の開発」の項2012

    • Author(s)
      中村貴史
    • Total Pages
      6
    • Publisher
      株式会社メディカルドゥ
    • Related Report
      2012 Research-status Report
  • [Remarks] 研究内容紹介

    • URL

      http://www.med.tottori-u.ac.jp/integbio/522/1198.html

    • Related Report
      2013 Final Research Report
  • [Remarks] ウイルスで新しいがん療法の開発をめざす

    • URL

      http://ganshien.umin.jp/public/research/main/nakamura/

    • Related Report
      2013 Final Research Report
  • [Remarks] がんナビ

    • URL

      http://medical.nikkeibp.co.jp/leaf/all/cancernavi/report/201301/528660_3.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 研究内容紹介

    • URL

      http://www.med.tottori-u.ac.jp/integbio/522/1198.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] ウイルスで新しいがん療法の開発をめざす

    • URL

      http://ganshien.umin.jp/public/research/main/nakamura/

    • Related Report
      2013 Annual Research Report
  • [Remarks] がんナビ

    • URL

      http://medical.nikkeibp.co.jp/leaf/all/cancernavi/report/201301/528660_3.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] ウイルスで新しいがん療法の開発をめざす

    • URL

      http://ganshien.umin.jp/public/research/main/nakamura/

    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 分裂促進因子活性化タンパク質キナーゼ依存性組換えワクシニアウイルス(MD-RVV)及びその使用2013

    • Inventor(s)
      中村貴史
    • Industrial Property Rights Holder
      国立大学法人鳥取大学、一般財団法人化学及血清療法研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-22
    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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