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Development of a new immunotherapy activating both cytotoxic and helper T cells against bladder cancer

Research Project

Project/Area Number 26293353
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Urology
Research InstitutionKyushu University (2015-2016)
Kumamoto University (2014)

Principal Investigator

Eto Masatoshi  九州大学, 医学(系)研究科(研究院), 教授 (90315078)

Co-Investigator(Kenkyū-buntansha) 河野 吉昭  熊本大学, その他の研究科, 講師 (30593793)
Co-Investigator(Renkei-kenkyūsha) NISHIMURA Yasuharu  熊本大学, 大学院生命科学研究部, 教授 (10156119)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywords癌 / 免疫学 / トランスレーショナルリサーチ
Outline of Final Research Achievements

In this study, we have succeeded in identifying 4 long peptides (LPs) that comprise from 22-29 amino acids originated from Bladder cancer tumor-associated antigens (TAA). We confirmed the immunogenecity of LPs from Bladder cancer TAA (TAA-LP) by induction of TAA-LP-specific helper T (Th) cells from healthy donors. We could also detect type 1 Th (Th1) cells specific for TAA-LPs from Bladder cancer patients. Using transgenic mice expressing human HLA-A2, we next showed the induction of cytotoxic T cells (CTLs) specific for short peptides (SPs) from Bladder cancer TAA (TAA-SP), even after immunization with TAA-LPs, indicating the cross-presentation to Th cells and CTLs by TAA-LPs. We also succeeded in the enhancemant of CTLs against TAA-SPs when combined with LPs, Th clones, and anti-PD-1 mAb, implicating the new strategy of combination therapy with TAA-LPs. The above results have indicated that TAA-LPs are effective, and can be a new treatment option for patients with Bladder cancer.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (11 results)

All 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 7 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder.2017

    • Author(s)
      Obara W, Eto M, Mimata H, Kohri K, Mitsuhata N, Miura I, Shuin T, Miki T, Koie T, Fujimoto H, Minami K, Enomoto Y, Nasu T, Yoshida T, Fuse H, Hara I, Kawaguchi K, Arimura A, Fujioka T.
    • Journal Title

      Ann Oncol

      Volume: 28 Issue: 4 Pages: 798-803

    • DOI

      10.1093/annonc/mdw675

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Suppressed Recurrent Bladder Cancer after Androgen Suppression with Androgen Deprivation Therapy or 5α-Reductase Inhibitor.2017

    • Author(s)
      Shiota M, Kiyoshima K, Yokomizo A, Takeuchi A, Kashiwagi E, Dejima T, Takahashi R, Inokuchi J, Tatsugami K, Eto M.
    • Journal Title

      J Urol

      Volume: 197 Issue: 2 Pages: 308-313

    • DOI

      10.1016/j.juro.2016.08.006

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Equol inhibits prostate cancer growth via degradation of the androgen receptor by Skp2.2016

    • Author(s)
      Itsumi M, Shiota M, Takeuchi A, Kashiwagi E, Inokuchi J, Tatsugami K, Kajioka S, Uchiumi T, Naito S, Eto M, Yokomizo A.
    • Journal Title

      Cancer Sci

      Volume: in press Pages: 327-331

    • DOI

      10.1016/j.intimp.2016.03.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] C5a receptor expression is associated with poor prognosis in urothelial cell carcinoma patients treated with radical cystectomy or nephroureterectomy.2016

    • Author(s)
      Wada Y, Maeda Y, Kubo T, Kikuchi K, Eto M, Imamura T
    • Journal Title

      Oncol Lett

      Volume: 12 Pages: 3995-4000

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] n Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy.2016

    • Author(s)
      Noguchi M, Matsumoto K, Uemura H, Arai G, Eto M, Naito S, Ohyama C, Nasu Y, Tanaka M, Moriya F, Suekane S, Matsueda S, Komatsu N, Sasada T, Yamada A, Kakuma T, Itoh K.
    • Journal Title

      Clin Cancer Res

      Volume: 22 Issue: 1 Pages: 54-60

    • DOI

      10.1158/1078-0432.ccr-15-1265

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prognostic Significance of Preoperative Urine Cytology in Low-grade Non-muscle-invasive Bladder Cancer.2016

    • Author(s)
      Kiyoshima K, Akitake M, Shiota M, Takeuchi A, Takahashi R, Inokuchi J, Tatsugami K, Yokomizo A, Eto M.
    • Journal Title

      Anticancer Res.

      Volume: 36 Pages: 799-802

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) polymorphisms exacerbate bladder cancer risk associated with alcohol drinking: Gene-environment interaction.2016

    • Author(s)
      Masaoka H, Ito H, Soga N, Hosono S, Oze I, Watanabe M, Tanaka H, Yokomizo A, Hayashi N, Eto M, Matsuo K.
    • Journal Title

      Carcinogenesis

      Volume: Epub

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Identification of cancer-testis antigen (DEPDC1 and MPHOSPH1)-derived long peptides encompassing both CTL and HLA class II-restricted Th cell epitopes.2016

    • Author(s)
      Miki Nakane, Masatoshi Hirayama, Shohei Ueda, Mohammad Abu Sayem, Junji Yatsuda, Atsushi Irie, Satoru Senju, Masatoshi Eto, Hideki Nakayama and Yasuharu Nishimura
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベン ションセンター&ラグナガーデンホテル
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Antitumor activity of recombinant BCG secreting interleukin-15-Ag85B fusion protein against bladder cancer.2016

    • Author(s)
      Takeuchi A, Shiota M, Tatsugami K, Yokomizo A, Eto M
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] A randomized trial comparing two different retention periods of intravesical pirarubicin instillation for intermediate risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection.2016

    • Author(s)
      Kurahashi R, Kasejima Y, Kawano Y, Takahashi W, Yamaguchi T, Tanoue K, Sakakida H, Yatsuda J, Murakami Y, Sugiyama Y, Eto M
    • Organizer
      The 111th Annual Meeting AUA 2016
    • Place of Presentation
      San Diego Convention Center
    • Year and Date
      2016-05-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 低リスク筋層非浸潤性膀胱癌の規定因子に関する検討.2016

    • Author(s)
      秋武正和、清島圭二郎、塩田真己、武内在雄、高橋良輔、猪口淳一、立神勝則、横溝 晃、江藤正俊
    • Organizer
      第104回日本泌尿器科学会総会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-04-23
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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