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Novel vaccination targeting stem cells of cervical cancer

Research Project

Project/Area Number 17K11285
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionSapporo Medical University

Principal Investigator

Saito Tsuyoshi  札幌医科大学, 医学部, 教授 (90145566)

Co-Investigator(Kenkyū-buntansha) 鳥越 俊彦  札幌医科大学, 医学部, 教授 (20301400)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords子宮頸癌 / がん幹細胞 / 免疫療法 / 子宮頸がん / ワクチン療法 / 子宮体がん / ペプチドワクチン / CTL / HPV
Outline of Final Research Achievements

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are a small subpopulation of cancer cells that are tumorigenic and are resistant to treatments, thus they are focused as treatment targets. We have established sphere-cultured CSCs/CICs from primary human uterine cervical carcinoma, and we isolated several clones from CSCs/CICs in this study. Thus, BORIS sf6 is a cervical CSC/CIC-specific subfamily and has a role in the maintenance of cervical CSCs/CICs. A BORIS C34_24(9)-specific cytotoxic T cell (CTL) clone showed cytotoxicity for BORIS sf6-overexpressing cervical cancer cells. Taken together, the results indicate that the CT antigen BORIS sf6 is specifically expressed in cervical CSCs/CICs, that BORIS sf6 has a role in the maintenance of CSCs/CICs, and that BORIS C34_24(9) peptide is a promising candidate for cervical CSC/CIC-targeting immunotherapy.

Academic Significance and Societal Importance of the Research Achievements

子宮頸癌は比較的若い女性に好発する腫瘍で、これらの若年女性達の子宮頸癌での喪失は、家族の幸福を奪うばかりではなく社会的・経済的な損失も大きい。化学療法や放射線療法に抵抗性の腫瘍も少なくなく新しい治療が望まれるところである。今回の研究はがん幹細胞に対する免疫療法の確立をめざし、子宮がん細胞株から幹細胞を選別しこれに対する特異抗原を同定し免疫療法へ応用への可能性を検討し、蛋白の一部が免疫療法に使うことが出来うることを証明した。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (23 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (13 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Less correlation between mismatch repair proteins deficiency and decreased expression of HLA class I molecules in endometrial carcinoma: a different propensity from colorectal cancer.2020

    • Author(s)
      Mariya T, Kubo T, Hirohashi Y, Yanagawa J, Tabuchi Y, Matsuo K, Furumura K, Morita R, Nakatsugawa M, Kanaseki T, Tsukahara T, Hasegawa T, Saito T, Torigoe T.
    • Journal Title

      Medical Molecular Morphology

      Volume: 54 Issue: 1 Pages: 14-22

    • DOI

      10.1007/s00795-020-00254-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clonal analysis revealed functional heterogeneity in cancer stem-like cell phenotypes in uterine endometrioid adenocarcinoma.2019

    • Author(s)
      Tabuchi Y, Hirohashi Y, Hashimoto S, Mariya T, Asano T, Ikeo K, Kuroda T, Mizuuchi M, Murai A, Uno S, Kawai N, Kubo T, Nakatsugawa M, Kanaseki T, Tsukahara T, Saito T, Torigoe T.
    • Journal Title

      Exp Mol Pathol

      Volume: 106 Pages: 78-88

    • DOI

      10.1016/j.yexmp.2018.11.013

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ABCG2 expression is related to low 5-ALA photodynamic diagnosis (PDD) efficacy and cancer stem cell phenotype, and suppression of ABCG2 improves the efficacy of PDD2019

    • Author(s)
      Kawai Noriko、Hirohashi Yoshihiko、Ebihara Yuma、Saito Takuma、Murai Aiko、Saito Takahiro、Shirosaki Tomohide、Kubo Terufumi、Nakatsugawa Munehide、Kanaseki Takayuki、Tsukahara Tomohide、Shichinohe Toshiaki、Li Liming、Hirano Satoshi、Torigoe Toshihiko
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 5 Pages: 0216503-0216503

    • DOI

      10.1371/journal.pone.0216503

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Localization of Tricellular Tight Junction Molecule LSR at Midbody and Centrosome During Cytokinesis in Human Epithelial Cells2019

    • Author(s)
      Konno Takumi、Kohno Takayuki、Kikuchi Shin、Shimada Hiroshi、Satohisa Seiro、Takano Kenichi、Saito Tsuyoshi、Kojima Takashi
    • Journal Title

      Journal of Histochemistry & Cytochemistry

      Volume: 68 Issue: 1 Pages: 59-72

    • DOI

      10.1369/0022155419886263

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epithelial barrier dysfunction and cell migration induction via JNK/cofilin/actin by angubindin-12019

    • Author(s)
      Konno Takumi、Kohno Takayuki、Kikuchi Shin、Shimada Hiroshi、Satohisa Seiro、Saito Tsuyoshi、Kondoh Masuo、Kojima Takashi
    • Journal Title

      Tissue Barriers

      Volume: 8 Issue: 1 Pages: 1695475-1695475

    • DOI

      10.1080/21688370.2019.1695475

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transabdominal cerclage (TAC) for patients with ultra-short uterine cervix after uterine cervix surgery and its impact on pregnancy2017

    • Author(s)
      Ishioka Shinichi、Kim Miseon、Mizugaki Yuko、Kon Saori、Isoyama Kyoko、Mizuuchi Masahito、Morishita Miyuki、Baba Tsuyoshi、Sekiya Takao、Saito Tsuyoshi
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 44 Issue: 1 Pages: 61-66

    • DOI

      10.1111/jog.13487

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer.2017

    • Author(s)
      Shimada H, Abe S, Kohno K, Satohisa S, Konno T, Takahashi S, Hatakeyama T, Arimoto C, Kakuki T, Kaneko Y, Takano K, Saito T, Kojima T
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 10935-10935

    • DOI

      10.1038/srep37049

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of dilatation and curettage performed for spontaneous or induced abortion in the etiology of endometrial thinning2017

    • Author(s)
      Azumaguchi Atsushi、Henmi Hirofumi、Ohnishi Hirofumi、Endo Toshiaki、Saito Tsuyoshi
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 43 Issue: 3 Pages: 523-529

    • DOI

      10.1111/jog.13254

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rap1GAP inhibits tumor progression in endometrial cancer2017

    • Author(s)
      Tamate Masato、Tanaka Ryoichi、Osogami Hiroyuki、Matsuura Motoki、Satohisa Seiro、Iwasaki Masahiro、Saito Tsuyoshi
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 485 Issue: 2 Pages: 476-483

    • DOI

      10.1016/j.bbrc.2017.02.044

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ovarian high-grade endometrioid stromal sarcoma with YWHAE and NUTM2B rearrangements2017

    • Author(s)
      Kikuchi Noriaki、Sugita Shintaro、Nakanishi Katsuya、Sugawara Taro、Segawa Keiko、Ito Yumika、Kubo Terufumi、Fujita Hiromi、Hirano Hiroshi、Tanaka Ryoichi、Saito Tsuyoshi、Hasegawa Tadashi
    • Journal Title

      Pathol Int

      Volume: 67 Issue: 6 Pages: 327-329

    • DOI

      10.1111/pin.12542

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 深層学習を用いた子宮頸部細胞診人工知能診断支援システムの有用性について2020

    • Author(s)
      真里谷 奨 、南部 優太 、淺沼 広子 、廣橋 良彦2、岩崎 雅宏、藤 野 雄一 、鳥越 俊彦、齋藤 豪
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] GRIK2 は膀胱癌幹細胞に特異的な癌抗原の候補である2020

    • Author(s)
      宮田 遥、廣橋 良彦、金関 貴幸、時田 芹奈、鳥越 俊彦
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] プロテオゲノミクス HLA リガンドーム解析による結腸癌の HLA ク ラス II ネオアンチゲンの同定2020

    • Author(s)
      松本 哲、金関 貴幸、鳥越 俊彦
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ・An Education System for Board-Certified Fellows of the Japan Society of Clinical Cytology2019

    • Author(s)
      Tsuyoshi Saito
    • Organizer
      ICC 2019 20th International Congress of Cytology(May.5-9, 2019, Sydney, Australia)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ・子宮体癌細胞株におけるERαとBAG3発現の関連2019

    • Author(s)
      阿部 秀悦、岩崎 雅宏、西村 庸子、玉手 雅人、磯山 響子、秋元 太志、幅田 周太朗、寺田 倫子、小川 万梨絵、松浦 基樹、郷久 晴朗、齋藤 豪
    • Organizer
      第61回日本婦人科腫瘍学会学術講演会(新潟・2019年7月4日~6日)
    • Related Report
      2019 Research-status Report
  • [Presentation] ・The regulation of claudin-2 in endometriosis and endometrioid carcinoma cells2019

    • Author(s)
      Seiro Satohisa, Hiroshi Shimada, Takayuki Kohno1), Takumi Konno1), Taishi Akimoto, Masahiro Iwasaki, Masato Tamate, Motoki Matsuura, Takashi Kojima1), Tsuyoshi Saito1
    • Organizer
      ICC 2019 20th International Congress of Cytology(May.5-9, 2019, Sydney, Australia)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Local progression of endometrial cancer depends on microsatellite instability and HLA class I expression2018

    • Author(s)
      T. Mariya, Y. Hirohashi1), J. Yanakawa1), T. Akimoto, M. Matsuura, S. Satohisa, M. Teramoto, M. Iwasaki, T. Kubo1), T. Torigoe1), T. Saito
    • Organizer
      IGCS 17th Biennial Meeting of the International Gynecologic Cancer Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of claudin-2 on the malignancy of human endometrioid carcinoma.2018

    • Author(s)
      Seiro Satohisa, Tsuyoshi Saito
    • Organizer
      European Society of Gynaecological Oncology State of the Art Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Treatment and prognosis of recurrent uterine leiomyosarcomas in last 5 years.2018

    • Author(s)
      Tsuyoshi Saito, Ryoichi Tanaka1), Seiro Satohisa, Shuetsu Abe, Masahiro Iwasaki, Mizue Teramoto, Motoki Matsuura, Masato Tamate
    • Organizer
      European Society of Gynaecological Oncology State of the Art Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 子宮頸部腺癌でのチロシンキナーゼ型受容体の発現と分子標的治療への可能性2017

    • Author(s)
      秋元太志
    • Organizer
      第59回公益社団法人日本婦人科腫瘍学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] 3細胞間タイト結合分子LSRはAMOTに活性化されたHippo pathwayを介し子宮内膜癌の悪性化に 関与する2017

    • Author(s)
      郷久晴朗
    • Organizer
      第59回公益社団法人日本婦人科腫瘍学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] 子宮内膜癌(endometrioid adenocarcinoma)におけるタイト結合分子claudin-2の役割2017

    • Author(s)
      嶋田浩志
    • Organizer
      第49回日本臨床分子形態学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ・Types and multiple infection of HPV are related to viral persistence and CIN recurrence after laser surgery2017

    • Author(s)
      Akira Nishikawa
    • Organizer
      European Gynecological Oncology Congress (November.4-7, 2017, Vienna, Austria)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2022-01-27  

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