Updated on 2024/09/18

写真a

 
AKATSUKA Yoshiki
 
Organization
Graduate School of Medicine Center for Research of Laboratory Animals and Medical Research Engineering Division Designated Professor
Title
Designated Professor
Contact information
メールアドレス
External link

Degree 1

  1. 博士(医学) ( 1995.4   名古屋大学 ) 

Research Interests 6

  1. Gene-modified T cell therapy

  2. immunotherapy

  3. Tumor immunity

  4. allogeneic hematopoietic cell transplantation

  5. Leukemia

Research Areas 3

  1. Life Science / Hematology and medical oncology  / Allogeneic hematopoietic stem cell transplantation

  2. Life Science / Immunology  / Tumor immunology

  3. Life Science / Hematology and medical oncology  / Cellular immunotherapy

Current Research Project and SDGs 3

  1. Immunotherapy targeting blood cancer using allo-immune cells

  2. 新規遺伝子改変T細胞の開発

  3. 腫瘍微小環境の免疫学的解析

Research History 12

  1. Nagoya University Graduate School of Medicine   Division of Immunology   Designated Professor

    2018.8

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    Country:Japan

  2. Fujita Health University School of Immunology   Dep. of Hematology   Visiting Prosfessor

    2018.8

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    Country:Japan

  3. Fujita Health University   Dep. of Hematology   Professor of Hospital

    2014.4 - 2018.7

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    Country:Japan

  4. Aichi Cancer Center Res. Inst.   Div. of Immunology   Visiting Scientist

    2009.7 - 2019.3

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    Country:Japan

  5. Fujita Health University   Dep. of Hematology   Associate Professor

    2009.7 - 2014.3

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    Country:Japan

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Education 1

  1. Kagawa Medical University   Faculty of Medicine

    1980.4 - 1986.3

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    Country: Japan

Professional Memberships 12

  1. 日本内科学会

    1986

  2. 日本血液学会   評議員

    1987

  3. 日本がん免疫学会   理事、評議員、産官学委員会委員長(2024-)

    2000

  4. 日本輸血細胞治療学会   評議員

    1990

  5. 日本免疫学会

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Committee Memberships 16

  1. 日本血液疾患免疫療法学会   理事長  

    2020.7 - 2023.5   

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    Committee type:Academic society

  2. Asian Pacific Blood and Marrow Transplantation Group   Editor-in-Chief  

    2017.10   

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    Committee type:Other

  3. 日本がん免疫学会   理事  

    2017.4   

  4. 日本がん免疫学会   広報委員長  

    2016.4   

  5. 日本造血細胞移植学会   広報委員会委員長  

    2016.3   

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Awards 3

  1. Shimizu Prize

    2013   Japan Leukemia Fund  

    AKATSUKA Yoshiki

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    Award type:Award from publisher, newspaper, foundation, etc. 

  2. 一般研究賞

    2004   公益信託 日本白血病研究基金  

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    Award type:Award from publisher, newspaper, foundation, etc. 

  3. 平成12年度(第37回)学術研究助成金

    2002   大幸財団  

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    Award type:Award from publisher, newspaper, foundation, etc. 

 

Papers 93

  1. 特集 CAR-T細胞療法の最前線--現状と残された課題 はじめに

    赤塚 美樹

    医学のあゆみ   Vol. 288 ( 3 ) page: 181 - 181   2024.1

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    Publisher:医歯薬出版  

    DOI: 10.32118/ayu28803181

    CiNii Research

  2. Development of TCR-T cell therapy targeting mismatched HLA-DPB1 for relapsed leukemia after allogeneic transplantation Reviewed International journal

    Barakat Carolyne, Inagaki Yuichiro, Mizuno Shohei, Nishio Nobuhiro, Katsuyama Naoya, Sato Yoshie, Kobayashi Miki, Ozeki Kazutaka, Iida Hiroatsu, Tomita Akihiro, Sawa Masashi, Demachi-Okamura Ayako, Takahashi Yoshiyuki, Nishikawa Hiroyoshi, Akatsuka Yoshiki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 118 ( 2 ) page: 252 - 266   2023.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:International Journal of Hematology  

    Relapsed leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a significant challenge, with the re-emergence of the primary disease being the most frequent cause of death. Human leukocyte antigen (HLA)-DPB1 mismatch occurs in approximately 70% of unrelated allo-HSCT cases, and targeting mismatched HLA-DPB1 is considered reasonable for treating relapsed leukemia following allo-HSCT if performed under proper conditions. In this study, we established several clones restricted to HLA-DPB1*02:01, -DPB1*04:02, and -DPB1*09:01 from three patients who underwent HLA-DPB1 mismatched allo-HSCT using donor-derived alloreactive T cells primed to mismatched HLA-DPB1 in the recipient’s body after transplantation. A detailed analysis of the DPB1*09:01-restricted clone 2A9 showed reactivity against various leukemia cell lines and primary myeloid leukemia blasts, even with low HLA-DP expression. T cell receptor (TCR)-T cells derived from clone 2A9 retained the ability to trigger HLA-DPB1*09:01-restricted recognition and lysis of various leukemia cell lines in vitro. Our study demonstrated that the induction of mismatched HLA-DPB1 specific T cell clones from physiologically primed post-allo-HSCT alloreactive CD4+ T cells and the redirection of T cells with cloned TCR cDNA by gene transfer are feasible as techniques for future adoptive immunotherapy.

    DOI: 10.1007/s12185-023-03621-y

    Web of Science

    Scopus

    PubMed

  3. TCR-Like CAR-T Cells Targeting MHC-Bound Minor Histocompatibility Antigens. Invited Reviewed International journal

    Yoshiki Akatsuka

    Frontiers in immunology   Vol. 11   page: 257 - 257   2020.2

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Minor histocompatibility antigens (mHAgs) in allogeneic hematopoietic stem cell transplantation are highly immunogenic as they are foreign antigens and cause polymorphism between donors and recipients. Adoptive cell therapy with mHAg-specific T cells may be an effective option for therapy against recurring hematological malignancies following transplantation. Genetically modified T cells with T cell receptors (TCRs) specific to mHAgs have been developed, but formation of mispaired chimeric TCRs between endogenous and exogenous TCR chains may compromise their function. An alternative approach is the development of chimeric antigen receptor (CAR)-T cells with TCR-like specificity whose CAR transmembrane and intracellular domains do not compete with endogenous TCR for CD3 complexes and transmit their own activation signals. However, it has been shown that the recognition of low-density antigens by high-affinity CAR-T cells has poor sensitivity and specificity. This mini review focuses on the potential for and limitations of TCR-like CAR-T cells in targeting human leukocyte antigen-bound peptide antigens, based on their recognition mechanisms and their application in targeting mHAgs.

    DOI: 10.3389/fimmu.2020.00257

    Web of Science

    Scopus

    PubMed

  4. Construction and molecular characterization of a T-cell receptor-like antibody and CAR-T cells specific for minor histocompatibility antigen HA-1H. Reviewed

    Inaguma Y, Akahori Y, Murayama Y, Shiraishi K, Tsuzuki-Iba S, Endoh A, Tsujikawa J, Demachi-Okamura A, Hiramatsu K, Saji H, Yamamoto Y, Yamamoto N, Nishimura Y, Takahashi T, Kuzushima K, Emi N, Akatsuka Y

    Gene therapy   Vol. 21   page: 575-584   2014.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/gt.2014.30

    PubMed

  5. HapMap scanning of novel human minor histocompatibility antigens. Reviewed

    Kamei M, Nannya Y, Torikai H, Kawase T, Taura K, Inamoto Y, Takahashi T, Yazaki M, Morishima S, Tsujimura K, Miyamura K, Ito T, Togari H, Riddell SR, Kodera Y, Morishima Y, Takahashi T, Kuzushima K, Ogawa S, Akatsuka Y

    Blood   Vol. 113   page: 5041-5048   2009.5

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2008-07-171678

    PubMed

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Books 3

  1. 必修!腫瘍免疫学

    赤塚美樹, 西川博嘉( Role: Contributor ,  免疫抑制細胞(総論))

    金原出版株式会社  2022.4  ( ISBN:9784307102087

  2. みんなに役立つ造血細胞移植 3版 基礎編 9:GVL効果の発現機序

    赤塚 美樹( Role: Contributor ,  基礎編 9)

    医薬ジャーナル社  2016.6  ( ISBN:978-4-7532-2801-0

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    Total pages:807   Language:Japanese Book type:Scholarly book

  3. 造血細胞移植マニュアル

    赤塚 美樹( Role: Contributor ,  10-2 マイナー組織適合抗原 A マイナー組織適合抗原の基礎知識)

    日本医学館  2004.9  ( ISBN:978-4890445677

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    Total pages:559   Language:Japanese

MISC 24

  1. IV. T-cell Receptor-engineered T Cells

    Akatsuka Yoshiki

    Nihon Naika Gakkai Zasshi   Vol. 108 ( 7 ) page: 1384 - 1390   2019.7

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    Language:Japanese   Publisher:The Japanese Society of Internal Medicine  

    DOI: 10.2169/naika.108.1384

    CiNii Research

  2. Understanding the tumor microenvironment as a foundation for development of immunotherapy against multiple myeloma Invited

      Vol. 86 ( 1 ) page: 84 - 89   2023.1

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    Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

  3. 免疫チェックポイント阻害薬の血液系合併症と管理 Invited

    赤塚 美樹

    臨床血液   Vol. 64 ( 8 ) page: 782 - 790   2023.1

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    Authorship:Lead author   Language:Japanese  

  4. [Hematological immune-related adverse events of immune checkpoint inhibitors and their management]. Invited

    Akatsuka Y

    臨床血液   Vol. 64 ( 8 ) page: 782 - 790   2023

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    Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    DOI: 10.11406/rinketsu.64.782

    PubMed

  5. 不適合アロ抗原を認識するT細胞受容体を用いた移植後再発白血病に対する遺伝子改変T細胞の開発

    赤塚 美樹

    BIO Clinica   Vol. 37 ( 6 ) page: 75 - 81   2022.6

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    Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Presentations 109

  1. Development of T-cell receptor gene-modified T cells using PiggyBac transposon

    2022.6.12 

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    Event date: 2022.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  2. Tumor microenvironment and immune status in multiple myeloma Invited

    Yoshiki Akatsuka

    The 47th annual Meeting of the Japanese Society of Myeloma  2022.5.21 

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    Event date: 2022.5

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  3. 同種造血細胞移植後の再発白血病に対する新規アロ養子免疫療法の開発 Invited

    赤塚 美樹

    第41回日本炎症・再生医学会 シンポジウム12 再生医療時代における免疫制御  2020.7.9 

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    Event date: 2020.7

    Presentation type:Oral presentation (invited, special)  

  4. 免疫チェックポイント阻害療法の進歩 Invited

    赤塚美樹

    第81回日本血液学会学術集会 教育講演 EL2-2D  2019.10.12 

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    Event date: 2019.10

    Language:English   Presentation type:Oral presentation (invited, special)  

  5. CAR-T細胞療法の基礎と今後の臨床展開 Invited

    赤塚 美樹

    第67回日本輸血・細胞治療学会学術総会 教育講演2  2019.5.23 

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    Event date: 2019.5

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

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Works 2

  1. HapMap SN Scanner の公開

    2012

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    Work type:Database science  

    DOI: 10.1111/j.1399-0039.2012.01883.x

  2. 日本人に頻度の高いHLAクラスI遺伝子のcDNAの単離とバンキング(理化学研究所バイオリソースセンター)

    2002
    -
    2004

Research Project for Joint Research, Competitive Funding, etc. 13

  1. ケモテクノロジーによる移植後GVHDの制御とアロ抗原特異的T細胞輸注による選択的GVL効果の誘導研究

    Grant number:23ek0510042h0001  2023.4 - 2026.3

    日本医療研究開発機構(AMED) 移植医療技術開発研究事業  

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\22500000

  2. 同種造血細胞移植後の再発白血病に対する 新規アロ養子免疫療法の開発研究

    Grant number:19ek0510027h  2019.4 - 2022.3

    日本医療研究開発機構(AMED) 移植医療技術開発研究事業  

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\31200000 ( Direct Cost: \24000000 、 Indirect Cost:\7200000 )

  3. 同種移植後再発白血病を目的とした不適合HLA-DP分子を標的とした免疫療法の開発

    2022.8 - 2023.3

    第47回(2022年度)がんその他の悪性新生物研究助成 

    赤塚美樹

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    Authorship:Principal investigator  Grant type:Other

    Grant amount:\500000

  4. 同種移植後再発白血病に対する不適合HLA-DP型を標的とするCAR-T療法の開 発

    2020.4 - 2021.3

    日本血液学会研究助成 

    赤塚美樹

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\200000

  5. 免疫チェックポイント阻害剤有効例における細胞傷害性T細胞抗原の同定

    2019.4 - 2020.4

    第44回(2019年度)研究助成金  がんに関する基礎研究

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\250000

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KAKENHI (Grants-in-Aid for Scientific Research) 14

  1. Establishment of the system for predicting pituitary dysfunction induced by immune checkpoint inhibitors

    Grant number:22H03127  2022.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Coinvestigator(s) 

  2. Development of CAR-T cells to treat recurring leukemia post-HCT by targeting mismatched HLA-DP

    Grant number:21K08369  2021.4 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Principal investigator 

    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

  3. Development of immunotherapy against malignancies relapsed post-transplant using TCR-T cells specific for mismatched HLAs

    Grant number:18K08341  2018.4 - 2021.3

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

  4. Identification of autoantigens recognized by cytotoxic T-cells and responsible for the pathogenesis of aplastic anemia.

    Grant number:15K09512  2015.4 - 2018.3

    Akatsuka Yoshiki

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    We attempted to identify antigens recognized by HLA-B*40:02-restricted cytotoxic T lymphocytes (CTLs) that might be related to the pathogenesis of aplastic anemia. Because the CTLs exerted cytotoxic activity on K562 cells transduced with HLA-B*40:02, we prepared cDNA libraries from messenger RNA extracted from K562. After extensive screening, a cDNA clone that stimulated interferon-gamma release from one of the CTLs was found. The cDNA was encoded by OS9 whose protein is known to be located in the endoplasmic reticulum and also involved in the hypoxic stress, implicating the potential involvement in the pathogenesis of aplastic anemia. The minimum epitope sequence was composed of 11 amino acids: MAAETLLSSLL. Using the peptide, functional analyses are ongoing. An antigen recognized by another CTL with suppressive function in hematopoietic cells has not been identified, even after screening more than 100,000 cDNA clones.

  5. 再生不良性貧血におけるゲノム異常を利用した造血抑制因子の同定(分担)

    Grant number: 24390243  2012.4 - 2015.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    中尾 眞二、赤塚美樹、松井 啓隆、高松 博幸、西内 巧

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\17940000 ( Direct Cost: \13800000 、 Indirect Cost:\4140000 )

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Industrial property rights 2

  1. 血清の製造方法

    赤塚美樹、高橋利忠

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    Applicant:愛知県

    Application no:特願2003-061398  Date applied:2003.3

    Announcement no:特開2004-269409  Date announced:2004.9

    Patent/Registration no:特許第4110285号 

  2. ウイルス特異的CTLの製造方法

    鈴木進、渡邉一絵、田路真悟、金律子、赤塚美樹、高橋利忠、葛島清隆

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    Applicant:株式会社医学生物学研究所

    Announcement no:WO2008/023786  Date announced:2008.8

 

Teaching Experience (On-campus) 2

  1. 免疫と生体防御

    2020

     詳細を見る

    感染免疫
    移植免疫
    免疫系の治療への応用(細胞を中心に)

  2. Molecular Pathology

    2020

Teaching Experience (Off-campus) 3

  1. 腫瘍学

    2018 藤田医科大学)

  2. 薬物治療学

    2015 名城大学薬学部)

  3. 血液内科学

    2010 藤田医科大学)

 

Social Contribution 4

  1. 第1部「造血幹細胞移植今昔物語」

    Role(s):Appearance, Presenter, Planner

    日本造血・免疫細胞療法学会  市民公開講座  2023.2

  2. 移植療法、免疫療法について.

    Role(s):Lecturer

    NPO法人血液情報広場つばさ  NPO法人血液情報広場つばさフォーラムin名古屋「血液がん」  2016.11

  3. がん免疫療法の新時代

    Role(s):Lecturer

    名城大学  薬学部卒後教育講演  2015.6

  4. Adoptive Immunotherapy Using CTLs Against Minor Antigens

    Role(s):Lecturer

    日本白血病研究基金・白血病研究基金を育てる会  白血病公開シンポジウム  2003.8