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Identification of novel minor histocompatibility antigens by next-generation sequencing in allogeneic stem cell transplantation patients

Research Project

Project/Area Number 16K09883
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKurume University

Principal Investigator

Koji Nagafuji  久留米大学, 医学部, 教授 (60343323)

Co-Investigator(Kenkyū-buntansha) 水野 晋一  九州大学, 医学研究院, 教授 (40569430)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords造血幹細胞移植 / 組織適合抗原 / マイナー組織適合性抗原 / 遺伝子解析 / 造血幹細胞移植学
Outline of Final Research Achievements

In allogeneic stem cell transplantation, the amino acid differences in proteins by SNPs (single nucleotide polymorphism) can cause immune responses, such as graft versus host disease (GVHD) and graft versus leukemia (GVL) effect. These minor histocompatibility antigens (mHAs) play an important role in eradicating leukemia cells after transplantation. However, only a small number of mHAs have been discovered and the identification of novel mHAs has been required. In this study, we developed a novel method for identification of mHAs by using next-generation sequencer. We applied whole exome sequencing for a donor and recipient, and extracted SNPs to each other. To narrow down the candidate genes of mHAs, non-synonymous SNPs are subject to be evaluated by HLA binding prediction algorithm. This study will enable us to identify novel mHAs in each pair of donor and recipient of transplantation, and will be useful for the development of an individualized immunotherapy based on mHAs.

Academic Significance and Societal Importance of the Research Achievements

次世代シーケンサーによる新たなマイナー組織抗原の同定は、移植片対宿主病(GVHD)や移植片対白血病効果(GVL)の予測に基づいた適切なドナー選択や、マイナー組織抗原を標的としたワクチンや養子免疫療法による個別化免疫療法につながるであろう。また、血液系腫瘍のみならず固形腫瘍においても選択的にGVT(Graft versus tumor)効果を誘導することで抗腫瘍効果を誘導し得る可能性があり、臨床への応用が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results)

  • [Journal Article] Myeloablative and reduced-intensity conditioning in HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide2018

    • Author(s)
      Sugita Junichi、on behalf of the Japan Study Group for Cell Therapy and Transplantation (JSCT)、Kagaya Yusuke、Miyamoto Toshihiro、Shibasaki Yasuhiko、Nagafuji Koji、Ota Shuichi、Furukawa Tatsuo、Nara Miho、Akashi Koichi、Taniguchi Shuichi、Harada Mine、Matsuo Keitaro、Teshima Takanori
    • Journal Title

      Bone Marrow Transplantation

      Volume: 54 Issue: 3 Pages: 432-441

    • DOI

      10.1038/s41409-018-0279-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prospective randomization of post-remission therapy comparing autologous peripheral blood stem cell transplantation versus high-dose cytarabine consolidation for acute myelogenous leukemia in first remission2017

    • Author(s)
      Miyamoto Toshihiro、For the Japan Study Group for Cell Therapy and Transplantation (JSCT)、Nagafuji Koji、Fujisaki Tomoaki、Uchida Naoyuki、Matsue Kosei、Henzan Hideho、Ogawa Ryosuke、Takase Ken、Aoki Takatoshi、Hidaka Michihiro、Teshima Takanori、Taniguchi Shuichi、Akashi Koichi、Harada Mine
    • Journal Title

      International Journal of Hematology

      Volume: 107 Issue: 4 Pages: 468-477

    • DOI

      10.1007/s12185-017-2389-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Notch1 expression is regulated at the post-transcriptional level by the 3′ untranslated region in hematopoietic stem cell development2017

    • Author(s)
      Mizuno Shinichi、Iino Tadafumi、Ozawa Hidetoshi、Arinobu Yojiro、Chong Yong、Akashi Koichi
    • Journal Title

      International Journal of Hematology

      Volume: 107 Issue: 3 Pages: 311-319

    • DOI

      10.1007/s12185-017-2358-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of clinicopathological characteristics between T-cell prolymphocytic leukemia and peripheral T-cell lymphoma, not otherwise specified.2017

    • Author(s)
      Kawamoto K, Miyoshi H, Yanagida E, Yoshida N, Kiyasu J, Kozai Y, Morikita T, Kato T, Suzushima H, Tamura S, Muta T, Kato K, Eto T, Seki R, Nagafuji K, Sone H, Takizawa J, Seto M, Ohshima K.
    • Journal Title

      Eur J Haematol.

      Volume: 98 Issue: 5 Pages: 459-466

    • DOI

      10.1111/ejh.12856

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful autologous peripheral blood stem cell transplantation in primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma.2017

    • Author(s)
      Saruta H, Ohata C, Oku E, Natsuaki Y, Ohshima K, Nagafuji K, Nakama T.
    • Journal Title

      J Dtsch Dermatol Ges.

      Volume: 15 Issue: 4 Pages: 440-442

    • DOI

      10.1111/ddg.13084

    • Related Report
      2016 Research-status Report
    • Peer Reviewed

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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