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Identification of paptide vaccine target in gynecologic cancer based on mRNA sewquencing

Research Project

Project/Area Number 17K16865
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionNihon University (2018)
Saitama Medical University (2017)

Principal Investigator

IKEDA Yuji  日本大学, 医学部, 助教 (80713453)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsがん精巣抗原 / 免疫療法 / 婦人科癌 / ペプチドワクチン / アンチゲン
Outline of Final Research Achievements

Firstly, mRNA sequencing data obtained from 582 samples of endometrial cancer and 53 control samples from 31 normal organs were extracted from cancer genome atlas (TCGA) database and Genotype-Tissue Expression project, respectively. After filtering of protein coding genes, 8 to 12 peptides with high binding affinity to HLA-A*24 and -A*02 alleles were identified. Analysis of binding affinity revealed that 21 and 146 peptides derived-from ten genes of interest showed high binding affinity to those HLA. Remarkably, RGPD6 is the most reliable candidate target. Secondly, we conducted a phase I dose-escalation trial using a mixture of 5 peptides to vaccinate cervical cancer patients with HLA-A*2402. Interferon-γ enzyme-linked immunospot assays for each of the 5 antigens showed that 8 (89%) and 7 (78%) patients had high T-cell responses to FOXM1 and MELK, respectively. As a result, RGPG6, FOXM1 and MELK are seemed to be a strong candidate of immunotherapeutic target for gynecologic cancers.

Academic Significance and Societal Importance of the Research Achievements

今回同定されたがんの特異性をターゲットとした免疫療法の開発は直接的にがん細胞を攻撃するアクセルの役割を担う事が大いに期待される。即ちこれらのターゲットを認識するT細胞を患者に投与する事で、がんを特異的に攻撃する免疫システムの構築が出来る可能性がある。加えて将来的には現在旺盛なチェックポイント阻害薬(免疫機構のブレーキを解除する意義がある)を併用する事でよりその効果も高める可能性があり、今後の研究開発の進展が期待される。

Report

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

    (10 results)

All 2019 2018 2017

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Phase I Study of Multiple Epitope Peptide Vaccination in Patients With Recurrent or Persistent Cervical Cancer2018

    • Author(s)
      Hasegawa K, Ikeda Y, Kunugi Y, Kurosaki A, Imai Y, Kohyama S, Nagao S, Kozawa E, Yoshida K, Tsunoda T, Nakamura Y, Fujiwara K.
    • Journal Title

      J Immunother

      Volume: 41(4) Issue: 4 Pages: 201-207

    • DOI

      10.1097/cji.0000000000000214

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effective Screening of T cells Recognizing Neoantigens and Construction of T-cell Receptor-engineered T cells2018

    • Author(s)
      Kato T, Matsuda T, Ikeda Y, Park JH, Leisegang M, Yoshimura S, Hikichi T, Harada M, Zewde M, Sato S, Hasegawa K, Kiyotani K, Nakamura Y
    • Journal Title

      Oncotarget

      Volume: 9(13) Issue: 13 Pages: 11009-11019

    • DOI

      10.18632/oncotarget.24232

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance of T cell clonality and expression levels of immune-related genes in endometrial cancer2017

    • Author(s)
      Ikeda Y, Kiyotani K, Yew PY, Sato S, Imai Y, Yamaguchi R, Miyano S, Fujiwara K, Hasegawa K, Nakamura Y
    • Journal Title

      Oncol Rep

      Volume: 37(5) Issue: 5 Pages: 2603-2610

    • DOI

      10.3892/or.2017.5536

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of the tumor T-cell receptor repertoire and immune microenvironment in patients with locoregionally advanced squamous cell carcinoma of the head and neck2017

    • Author(s)
      Saloura V, Fatima A, Zewde M, Kiyotani K, Brisson RJ, Park JH, Ikeda Y, Vougiouklakis T, Bao R, Seiwert TY, Cipriani NA, Lingen MW, Vokes EE, Nakamura Y.
    • Journal Title

      Clin Cancer Res

      Volume: 23(16) Issue: 16 Pages: 4897-4907

    • DOI

      10.1158/1078-0432.ccr-17-0103

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of the cryoablation-induced immune response in kidney cancer patients2017

    • Author(s)
      Kato T, Iwasaki T, Uemura M, Nagahara A, Higashihara H, Osuga K, Ikeda Y, Kiyotani K, Park JH, Nonomura N, Nakamura Y.
    • Journal Title

      Oncoimmunology

      Volume: 6(7)

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrated analysis of somatic mutations and immune microenvironment of multiple regions in breast cancers2017

    • Author(s)
      Kato T, Park JH, Kiyotani K, Ikeda Y, Miyoshi Y, Nakamura Y.
    • Journal Title

      Oncotarget

      Volume: 8(37) Issue: 37 Pages: 62029-62038

    • DOI

      10.18632/oncotarget.18790

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The frequency of neoantigens per somatic mutation rather than overall mutational load or number of predicted neoantigens per se is a prognostic factor in ovarian clear cell carcinoma2017

    • Author(s)
      Matsushita H, Hasegawa K, Oda K, Yamamoto S, Nishijima A, Imai Y, Asada K, Ikeda Y, Karasaki T, Fujiwara K, Aburatani H, Kakimi K.
    • Journal Title

      Oncoimmunology

      Volume: 6(8)

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification of endometrial cancer specific immunotherapeutic targets by comprehensive In Silico analysis2019

    • Author(s)
      Yuji Ikeda
    • Organizer
      American Association for Cancer Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of endometrial cancer specific immunotherapeutic targets by comprehensive In Silico analysis2019

    • Author(s)
      Yuji Ikeda
    • Organizer
      第71回日本産婦人科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Evaluation of neo-antigen specific CD8+ T cells in ascites of gynecologic cancer patients and identification of their T cell receptors using next generation sequencer2017

    • Author(s)
      Yuji Ikeda, Kosei Hasegawa, Sho Sato, Keiichi Fujiwara, Yusuke Nakamura
    • Organizer
      第69回日本産科婦人科学会学術講演会
    • Related Report
      2017 Research-status Report

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

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