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Development of the third generation oncolytic HSV-1 for control of lymph node metastasis and bone invasion in oral cancer

Research Project

Project/Area Number 17K17856
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Surgical dentistry
Tumor therapeutics
Research InstitutionOsaka University

Principal Investigator

Uchihashi Toshihiro  大阪大学, 歯学部附属病院, 医員 (60757839)

Research Collaborator Kogo Mikihiko  
Sugauchi Akinari  
Kurioka Kyoko  
Todo Tomoki  
Ino Yasushi  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsがんウイルス療法 / 口腔癌リンパ節転移 / 抗腫瘍免疫 / 口腔癌のウイルス療法 / ウイルス療法 / 口腔癌 / リンパ節転移 / 遺伝子治療 / 歯学
Outline of Final Research Achievements

In this study, we evaluated the therapeutic efficacy of T-B7-1 or T-mfIL-12, a triple mutated oncolytic HSV-1 expressing soluble murine B7-1, or oncolytic HSV-1 armed with murine interleukin 12 (IL-12)in orthotopic mouse tongue cancer model using KLN205-MUC1 cells. This model reproduces the stepwise development of the disease characterized by local lymph-node metastases followed by lung metastases.
The results suggest that T-B7-1 orT-mfIL-12 more prevents the progression of neck lymph node metastases than T-01, a control virus.

Academic Significance and Societal Importance of the Research Achievements

新たに作成したマウス口腔癌リンパ節転移モデルを用いて、免疫賦活化因子発現型第三世代がん治療用HSV-1は、原発巣に対して極めて有効な治療法であるのみならず、頸部リンパ節転移に対して 有効であることが明らかとなり(特に原発巣に投与した際の頸部微小転移に対して)、これらのウイルスを用いることで、これまで制御困難であった頸部リンパ節転移の制御、および口腔癌患者QOL の保持という口腔扁平上皮癌の治療において非常に重要な効果をもたらすことが期待された。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Isolation of cancer cells with augmented spheroid-forming capability using a novel tool equipped with removable filter.2018

    • Author(s)
      Fujibayashi E, Yabuta N, Nishikawa Y, Uchihashi T, Miura D, Kurioka K, Tanaka S, Kogo M, Nojima H.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 74 Pages: 33931-33946

    • DOI

      10.18632/oncotarget.26092

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ELAS1 induces apoptotic death in adenocarcinoma DU145 and squamous-cell carcinoma SAS cancer cells, but not in normal KD cells2017

    • Author(s)
      Uchihashi Toshihiro、Ota Kaori、Yabuno Yusuke、Ohno Shouichi、Fukushima Kohshiro、Naito Yoko、Kogo Mikihiko、Yabuta Norikazu、Nojima Hiroshi
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 49 Pages: 85868-85882

    • DOI

      10.18632/oncotarget.20696

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase.2017

    • Author(s)
      Fukushima K, Wang M, Naito Y, Uchihashi T, Kato Y, Mukai S, Yabuta N, Nojima H.
    • Journal Title

      Cell Cycle

      Volume: 16 Issue: 5 Pages: 415-427

    • DOI

      10.1080/15384101.2016.1241916

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] TGF-β-induced cell cycle arrest is associated with increased migration and metastasis of oral squamous carcinoma cells2019

    • Author(s)
      Kazuki Takahashi, Katarzyna Inoue, Yasuhiro Yoshimatsu, Atsushi Kaida, Kei Takahashi, Shimpei Kubota, Akinari Sugauchi, Toshihiro Uchihashi, Susumu Tanaka, Mikihiko Kogo, Masahiko Miura, Kohei Miyazono, Tetsuro Watabe
    • Organizer
      11th AACR-JCA Joint Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Highly motile oral squamous carcinoma cells responding to TGF-β are under cell cycle arrest2019

    • Author(s)
      Katarzyna A. Inoue, Kazuki Takahashi, Yasuhiro Yoshimatsu, Akinari Sugauchi, Kei Takahashi, Shimpei. Kubota, Toshihiro Uchihashi, Atsushi Kaida, Susumu Tanaka, Masahiko Miura, Mikihiko Kogo, Kohei Miyazono and Tetsuro Watabe
    • Organizer
      Keystone Symposia, Cancer Metastasis:The Role of Metabolism, Immunity and the Microenvironment
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The efficacy of G47Δ in treating mouse tongue cancer models2018

    • Author(s)
      Toshihiro Uchihashi, Akinari Sugauchi, Yasushi Ino, Mikihiko Kogo and Tomoki Todo
    • Organizer
      43rd AOMSI Conference, Chennai, 2018 (1stINDO-JAPAN OMS CONFERENCE)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Therapeutic efficacy of IL-12 expressing oncolytic HSV-1 for neck lymph node metastases in mouse tongue cancer model2018

    • Author(s)
      Kyoko Kurioka, Toshihiro Uchihashi, Akinari Sugauchi, Hirokazu Nakahara, Yasushi Ino, Mikihiko Kogo and Tomoki Todo
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 口腔扁平上皮癌細胞株SASにおけるEMTとSphere形成能との関連についての検討2017

    • Author(s)
      藤林えみ、田中晋、内橋俊大、薮野佑介、古郷幹彦
    • Organizer
      第71回 NPO法人 日本口腔科学学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] LATS and SLUG regulate a malignancy acquired by spiral EMT-MET pathway in oral cancer cells2017

    • Author(s)
      Emi Fujibayashi, Satomi Mukai, Toshihiro Uchihashi, Susumu Tanaka, Mikihiko Kogo and Norikazu Yabuta
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Efficacy of oncolytic HSV-1 armed with soluble B7-1 in a mouse model for lymph node metastases of tongue cancer2017

    • Author(s)
      Akinari Sugauchi, Toshihiro Uchihashi, Yasushi Ino, Mikihiko Kogo and Tomoki Todo
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 上顎正中過剰埋伏歯抜歯後早期に発生した集合性歯牙種の一例2017

    • Author(s)
      内橋俊大、栗岡恭子、須河内昭成、平岡慎一郎、薮野佑介、藤林えみ、相川友直、古郷幹彦
    • Organizer
      第36回日本口腔腫瘍学会総会・学術総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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