Updated on 2021/03/26

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 4

  1. Gene-modified T cell therapy

  2. immunotherapy

  3. allogeneic hematopoietic cell transplantation

  4. Tumor immunity

Research Areas 3

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

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

  3. Life Science / Immunology  / Tumor immunology

Current Research Project and SDGs 3

  1. 新規遺伝子改変T細胞の開発

  2. 腫瘍微小環境の免疫学的解析

  3. Immunotherapy targeting blood cancer using allo-immune cells

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

  6. Aichi Cancer Center Research Institute   Div. of Immunology   Section Head

    2004.4 - 2009.6

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    Country:Japan

  7. Aichi Cancer Center Resarch Institute   Div. of Immunology

    2000.7 - 2004.3

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    Country:Japan

  8. Fred Hutchinson Cancer Res. Ctr.   Immunology   Research Associate

    1995.4 - 2000.4

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    Country:United States

  9. Nagoya University School of Medicine   First Dep. of Internal Medicine

    1992.12 - 1995.3

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    Country:Japan

  10. 癌研究会附属病院   化学療法科   医員

    1991.8 - 1992.12

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    Country:Japan

  11. Japanese Red Cross Nagoya First Hospital   Department of Hematology

    1986.4 - 1992.7

  12. 名古屋第一赤十字病院   血液内科   医員

    1986.4 - 1991.7

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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 11

  1. 日本内科学会

  2. 日本血液学会   評議員

  3. 日本がん免疫学会   理事、評議員、広報委員会委員長

  4. 日本輸血細胞治療学会   評議員

  5. 日本免疫学会

  6. 日本癌学会

  7. 日本臨床腫瘍学会

  8. 日本造血幹細胞移植学会   評議員、理事、広報委員会委員長

  9. 血液疾患免疫療法学会   理事長、理事、評議員

  10. American Society of Hematology

  11. Asia Pacific Blood and Marrow Transplantation Group

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Committee Memberships 14

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

    2017.10   

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    Committee type:Other

  2. 日本がん免疫学会   理事  

    2017.4   

  3. 日本がん免疫学会   広報委員長  

    2016.4   

  4. 日本造血細胞移植学会   広報委員会委員長  

    2016.3   

  5. 日本輸血・細胞治療学会   評議員  

    2014.4   

  6. 日本造血細胞移植学会   編集委員会委員長  

    2012.3 - 2016.3   

  7. 日本血液疾患免疫療法学会   理事 (2020~理事長)  

    2012   

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    Committee type:Academic society

  8.   Editorial Board Members  

    2011.1   

  9. 日本癌学会   評議員  

    2010.4   

  10. 日本造血細胞移植学会   理事  

    2010.3   

  11. 日本血液疾患免疫療法学会   評議員(運営委員)  

    2009   

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    Committee type:Academic society

  12. 日本がん免疫学会   評議員  

    2007.4   

  13. 日本血液学会   評議員  

    2004.4   

  14. 日本造血細胞移植学会   評議員  

    2002.3   

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Awards 7

  1. 第44回(2019年度)研究助成金(がんに関する基礎研究)

    2019   公益財団法人愛知県がん研究振興会  

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

  2. 第42回(平成29年度)研究助成金 (がんに関する基礎研究)

    2017   公益財団法人 愛知県がん研究振興会  

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

  3. Shimizu Prize

    2013   Japan Leukemia Fund  

    AKATSUKA Yoshiki

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

  4. 平成20年度(第41回)がん研究助成

    2008   財団法人 がん研究振興財団  

  5. 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. 

  6. 第28回(平成15年度)がんその他の悪性新生物研究助成

    2003   財団法人愛知県がん研究振興会  

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

  7. 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. 

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Papers 87

  1. 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

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  2. 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

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  3. 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

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  4. Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA. Reviewed

    Kawase T, Nannya Y, Torikai H, Yamamoto G, Onizuka M, Morishima S, Tsujimura K, Miyamura K, Kodera Y, Morishima Y, Takahashi T, Kuzushima K, Ogawa S, Akatsuka Y

    Blood   Vol. 111   page: 3286-3294   2008.3

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2007-10-118950

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  5. Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen. Reviewed

    Kawase T, Akatsuka Y, Torikai H, Morishima S, Oka A, Tsujimura A, Miyazaki M, Tsujimura K, Miyamura K, Ogawa S, Inoko H, Morishima Y, Kodera Y, Kuzushima K, Takahashi T

    Blood   Vol. 110   page: 1055-1063   2007.8

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2007-02-075911

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  6. A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene. Reviewed

    Torikai H, Akatsuka Y, Miyazaki M, Warren EH 3rd, Oba T, Tsujimura K, Motoyoshi K, Morishima Y, Kodera Y, Kuzushima K, Takahashi T

    Journal of immunology (Baltimore, Md. : 1950)   Vol. 173   page: 7046-7054   2004.12

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  7. The immunogenicity of a new human minor histocompatibility antigen results from differential antigen processing. Reviewed

    Brickner AG, Warren EH, Caldwell JA, Akatsuka Y, Golovina TN, Zarling AL, Shabanowitz J, Eisenlohr LC, Hunt DF, Engelhard VH, Riddell SR

    The Journal of experimental medicine   Vol. 193   page: 195-206   2001.1

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.193.2.195

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  8. A simple method to distinguish residual elotuzumab from monoclonal paraprotein in immunofixation assays for multiple myeloma patients Reviewed

    Chen Shurui, Kiguchi Toru, Nagata Yasuyuki, Tamai Yotaro, Ikeda Takeshi, Kajiya Ryoko, Ono Takaaki, Sugiyama Daisuke, Nishikawa Hiroyoshi, Akatsuka Yoshiki

    INTERNATIONAL JOURNAL OF HEMATOLOGY     2021.1

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    Publisher:International Journal of Hematology  

    DOI: 10.1007/s12185-021-03088-9

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  9. Improving TCR affinity on 293 T cells. Reviewed International journal

    Ohta R, Demachi-Okamura A, Akatsuka Y, Fujiwara H, Kuzushima K

    Journal of immunological methods   Vol. 466   page: 1 - 8   2019.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jim.2018.11.010

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  10. Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas.

    Leukemia     2019.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41375-019-0380-5

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  11. Comparison of the tube test and column agglutination techniques for anti-A/-B antibody titration in healthy individuals. Reviewed International journal

    Matsuura H, Akatsuka Y, Matsuno T, Sugiura Y, Arakawa S, Oikawa S, Yoshida J, Kosugi M, Emi N

    Vox sanguinis   Vol. 113 ( 8 ) page: 787 - 794   2018.11

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

    DOI: 10.1111/vox.12713

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  12. Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1–RUNX1T1 leukemia with t(8;12;21) Reviewed International journal

    Akihiro Abe, Yukiya Yamamoto, Akira Katsumi, Akinao Okamoto, Masutaka Tokuda, Yoko Inaguma, Kiyoko Yamamoto, Masamitsu Yanada, Tadaharu Kanie, Akihiro Tomita, Yoshiki Akatsuka, Masataka Okamoto, Toshiki Kameyama, Akila Mayeda, Nobuhiko Emi

    International Journal of Hematology   Vol. 108 ( 2 ) page: 208 - 212   2018.8

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    © 2017, The Japanese Society of Hematology. Variant chromosomal translocations associated with t(8;21) are observed in 3–4% of acute myeloid leukemia (AML) cases with a RUNX1–RUNX1T1 fusion gene. However, the molecular events that occur in variants of t(8;21) are not well characterized. In the present study, we report genetic features of a variant three-way translocation of t(8;12;21)(q22;p11;q22) in a patient with AML. In this patient, leukemia cells lacked azurophilic granules, which does not correspond with the classic features of t(8;21). RNA-seq analysis revealed that TM7SF3 at 12p11 was fused to VPS13B at 8q22 and VPS13B to RUNX1, in addition to RUNX1–RUNX1T1. VPS13B was located near RUNX1T1 and both were localized at the same chromosomal bands. The reading frames of TM7SF3 and VPS13B did not match to those of VPS13B and RUNX1, respectively. Disruption of VPS13B causes Cohen syndrome, which presents intermittent neutropenia with a left-shifted granulopoiesis in the bone marrow. Disruption of VPS13B may thus cause the unusual features of RUNX1–RUNX1T1 leukemia. Our case indicates that rearrangement of VPS13B may be additional genetic events in variant t(8;21).

    DOI: 10.1007/s12185-017-2387-x

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  13. Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack. Reviewed International journal

    Espinoza JL, Elbadry MI, Chonabayashi K, Yoshida Y, Katagiri T, Harada K, Nakagawa N, Zaimoku Y, Imi T, Hassanein HA, Khalifa A Noreldin A, Takenaka K, Akashi K, Hamana H, Kishi H, Akatsuka Y, Nakao S

    Blood advances   Vol. 2 ( 4 ) page: 390 - 400   2018.2

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    DOI: 10.1182/bloodadvances.2017013342

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  14. Successful treatment with allogeneic stem cell transplantation followed by DLI and TKIs for e6a2 BCR-ABL -positive acute myeloid leukaemia: A case report and literature review Reviewed International journal

    Yasuhiko Harada, Satoshi Nishiwaki, Takumi Sugimoto, Koichi Onodera, Tatsunori Goto, Takahiko Sato, Sonoko Kamoshita, Naomi Kawashima, Aika Seto, Shingo Okuno, Satomi Yamamoto, Toshihiro Iwasaki, Yukiyasu Ozawa, Koichi Miyamura, Yoshiki Akatsuka, Isamu Sugiura

    Medicine (United States)   Vol. 96 ( 50 ) page: e9160   2017.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Lippincott Williams and Wilkins  

    Rationale:Patients with the e6a2 BCR-ABL transcript, 1 of the atypical transcripts, have been reported to have a poor prognosis, and allogeneic stem cell transplantation (ASCT) can be considered as additional therapy. However, long-term survival after ASCT for this disease is rare.Patient concerns:This report concerns a 55-year-old female patient with e6a2 BCR-ABL-positive acute myeloid leukemia including the outcome of ASCT followed by donor lymphocyte infusion (DLI).Diagnoses:The breakpoint was confirmed by direct sequencing. Her minimal residual disease could be detected by nested reverse-transcription polymerase chain reaction using primers for the minor BCR-ABL (e1a2) transcript.Interventions:Treatment with tyrosine kinase inhibitors (TKIs) and ASCT followed by DLI.Outcomes:Despite multiple cytogenetic and molecular relapses after ASCT, she remains in molecular remission at 46 months after ASCT.Lessons:This case indicates the efficacy of the combination of the graft-versus-leukemia effect and TKIs for e6a2 BCR-ABL-positive acute leukemia. When the Philadelphia chromosome with an unusual chromosomal breakpoint is suggested, we should clarify the breakpoint because that information can aid molecular assessments and decisions to provide an additional or alternative therapy.

    DOI: 10.1097/MD.0000000000009160

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  15. Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS Reviewed International journal

    Isao Tawara, Shinichi Kageyama, Yoshihiro Miyahara, Hiroshi Fujiwara, Tetsuya Nishida, Yoshiki Akatsuka, Hiroaki Ikeda, Kazushi Tanimoto, Seitaro Terakura, Makoto Murata, Yoko Inaguma, Masahiro Masuya, Naoki Inoue, Tomohide Kidokoro, Sachiko Okamoto, Daisuke Tomura, Hideto Chono, Ikuei Nukaya, Junichi Mineno, Tomoki Naoe, Nobuhiko Emi, Masaki Yasukawa, Naoyuki Katayama, Hiroshi Shiku

    BLOOD   Vol. 130 ( 18 ) page: 1985 - 1994   2017.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC HEMATOLOGY  

    Wilms' tumor 1 (WT1) is constantly expressed in leukemic cells of acute leukemia and myelodysplastic syndrome (MDS). A T-cell receptor (TCR) that specifically reacts with WT1 peptide in the context of HLA-A*24:02 has been identified. We conducted a first-inhuman trial of TCR-gene transduced T-cell (TCR-T-cell) transfer in patients with refractory acute myeloblastic leukemia (AML) and high-risk MDS to investigate the safety and cell kinetics of the T cells. The WT1-specific TCR-gene was transduced to T cells using a retroviral vector encoding small interfering RNAs for endogenous TCR genes. The T cells were transferred twice with a 4-week interval in a dose-escalating design. After the second transfer, sequential WT1 peptide vaccines were given. Eight patients, divided into 2 dose cohorts, received cell transfer. No adverse events of normal tissue were seen. The TCR-T cells were detected in peripheral blood for 8 weeks at levels proportional to the dose administered, and in 5 patients, they persisted throughout the study period. The persisting cells maintained ex vivo peptide-specific immune reactivity. Two patients showed transient decreases in blast counts in bone marrow, which was associated with recovery of hematopoiesis. Four of 5 patients who had persistent T cells at the end of the study survived more than 12 months. These results suggest WT1-specific TCR-T cells manipulated by ex vivo culture of polyclonal peripheral lymphocytes survived in vivo and retained the capacity to mount an immune reaction to WT1.

    DOI: 10.1182/blood-2017-06-791202

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  16. The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B-cell lymphoma patients Reviewed International journal

    Akinao Okamoto, Masamitsu Yanada, Yoko Inaguma, Masutaka Tokuda, Satoko Morishima, Tadaharu Kanie, Yukiya Yamamoto, Shuichi Mizuta, Yoshiki Akatsuka, Tetsushi Yoshikawa, Yoshikazu Mizoguchi, Shigeo Nakamura, Masataka Okamoto, Nobuhiko Emi

    Hematological Oncology   Vol. 35 ( 1 ) page: 87 - 93   2017.3

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    © 2015 John Wiley & Sons, Ltd. Epstein–Barr virus (EBV)-encoded small RNA in situ hybridization (EBER-ISH) is a widely accepted method to evaluate EBV involvement in diffuse large B-cell lymphoma (DLBCL), although little is known regarding associations between EBV DNA load and the EBER status and whether EBV DNA load data provide additional clinical information. In this study, we quantified EBV DNA load in diagnostic specimens from DLBCL patients diagnosed at our hospital to evaluate clinical implications of EBV DNA load in diagnostic specimens as contrasted with EBER-ISH. Among 140 DLBCL patients without underlying immunodeficiency, 51 were evaluable for both EBER and EBV DNA load, 83 for EBER only and one for EBV DNA load only. The median EBV DNA load was 708 copies/μg. Although EBV DNA load was significantly higher for EBER-positive patients than for EBER-negative patients (p<0.001), EBV DNA was detected in up to 72% of EBERnegative patients. Progression-free survival and overall survival were significantly worse for patients with EBV DNA load above 700 copies/μg than for those with EBV DNA load below 700 copies/μg (p = 0.009 and p = 0.003); they were also significantly worse for EBER-positive patients than for EBER-negative patients (p<0.001 and p = 0.001). Even among EBER-negative patients, higher EBV DNA load conferred worse progression-free survival and overall survival (p = 0.041 and p = 0.013). These findings indicate that EBV DNA load in diagnostic specimens is not a simple surrogate for the EBER status and may be a potential biomarker associated with EBV involvement and prognosis in DLBCL.

    DOI: 10.1002/hon.2245

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  17. Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers. Reviewed

    Kataoka K, Shiraishi Y, Takeda Y, Sakata S, Matsumoto M, Nagano S, Maeda T, Nagata Y, Kitanaka A, Mizuno S, Tanaka H, Chiba K, Ito S, Watatani Y, Kakiuchi N, Suzuki H, Yoshizato T, Yoshida K, Sanada M, Itonaga H, Imaizumi Y, Totoki Y, Munakata W, Nakamura H, Hama N, Shide K, Kubuki Y, Hidaka T, Kameda T, Masuda K, Minato N, Kashiwase K, Izutsu K, Takaori-Kondo A, Miyazaki Y, Takahashi S, Shibata T, Kawamoto H, Akatsuka Y, Shimoda K, Takeuchi K, Seya T, Miyano S, Ogawa S

    Nature   Vol. 534 ( 7607 ) page: 402-406   2016.6

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    DOI: 10.1038/nature18294

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  18. TP53 mutations in older adults with acute myeloid leukemia. Reviewed

    Yanada M, Yamamoto Y, Iba S, Okamoto A, Inaguma Y, Tokuda M, Morishima S, Kanie T, Mizuta S, Akatsuka Y, Okamoto M, Emi N

    International journal of hematology   Vol. 103 ( 4 ) page: 429-435   2016.4

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-016-1942-1

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  19. ETV6-LPXN fusion transcript generated by t(11;12)(q12.1;p13) in a patient with relapsing acute myeloid leukemia with NUP98-HOXA9. Reviewed

    Abe A, Yamamoto Y, Iba S, Kanie T, Okamoto A, Tokuda M, Inaguma Y, Yanada M, Morishima S, Mizuta S, Akatsuka Y, Okamoto M, Kameyama T, Mayeda A, Emi N

    Genes, chromosomes & cancer   Vol. 55 ( 3 ) page: 242-250   2016.3

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/gcc.22327

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  20. Induction of HLA-B*40:02-restricted T cells possessing cytotoxic and suppressive functions against haematopoietic progenitor cells from a patient with severe aplastic anaemia. Reviewed

    Inaguma Y, Akatsuka Y, Hosokawa K, Maruyama H, Okamoto A, Katagiri T, Shiraishi K, Murayama Y, Tsuzuki-Iba S, Mizutani Y, Nishii C, Yamamoto N, Demachi-Okamura A, Kuzushima K, Ogawa S, Emi N, Nakao S

    British journal of haematology   Vol. 172 ( 1 ) page: 131-134   2016.1

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    DOI: 10.1111/bjh.13464

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  21. Genome-wide surveillance of mismatched alleles for graft-versus-host disease in stem cell transplantation. Reviewed

    Sato-Otsubo A, Nannya Y, Kashiwase K, Onizuka M, Azuma F, Akatsuka Y, Ogino Y, Satake M, Sanada M, Chiba S, Saji H, Inoko H, Kennedy GC, Yamamoto K, Morishima S, Morishima Y, Kodera Y, Sasazuki T, Ogawa S, Japan Marrow Donor Program.

    Blood   Vol. 126 ( 25 ) page: 2752-2763   2015.12

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2015-03-630707

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  22. Prognostic significance of Epstein-Barr virus DNA detection in pretreatment serum in diffuse large B-cell lymphoma. Reviewed

    Okamoto A, Yanada M, Miura H, Inaguma Y, Tokuda M, Morishima S, Kanie T, Yamamoto Y, Mizuta S, Akatsuka Y, Yoshikawa T, Mizoguchi Y, Nakamura S, Okamoto M, Emi N

    Cancer science   Vol. 106 ( 11 ) page: 1576-1581   2015.11

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    DOI: 10.1111/cas.12812

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  23. The fate of patients with acute myeloid leukemia not undergoing induction chemotherapy. Reviewed

    Yanada M, Okamoto A, Inaguma Y, Tokuda M, Morishima S, Kanie T, Yamamoto Y, Mizuta S, Akatsuka Y, Okamoto M, Emi N

    International journal of hematology   Vol. 102 ( 1 ) page: 35-40   2015.7

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-015-1786-0

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  24. Generation of mouse pluripotent stem cell-derived proliferating myeloid cells as an unlimited source of functional antigen-presenting cells. Reviewed

    Zhang R, Liu TY, Senju S, Haruta M, Hirosawa N, Suzuki M, Tatsumi M, Ueda N, Maki H, Nakatsuka R, Matsuoka Y, Sasaki Y, Tsuzuki S, Nakanishi H, Araki R, Abe M, Akatsuka Y, Sakamoto Y, Sonoda Y, Nishimura Y, Kuzushima K, Uemura Y

    Cancer immunology research   Vol. 3 ( 6 ) page: 668-677   2015.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1158/2326-6066.CIR-14-0117

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  25. NUP214-RAC1 and RAC1-COL12A1 Fusion in Complex Variant Translocations Involving Chromosomes 6, 7 and 9 in an Acute Myeloid Leukemia Case with DEK-NUP214. Reviewed

    Abe A, Yamamoto Y, Iba S, Okamoto A, Tokuda M, Inaguma Y, Yanada M, Morishima S, Kanie T, Tsuzuki M, Akatsuka Y, Mizuta S, Okamoto M, Kameyama T, Mayeda A, Emi N

    Cytogenetic and genome research   Vol. 146 ( 4 ) page: 279-284   2015

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1159/000441464

    PubMed

  26. Adoptive transfer of genetically engineered WT1-specific cytotoxic T lymphocytes does not induce renal injury. Reviewed

    Asai H, Fujiwara H, Kitazawa S, Kobayashi N, Ochi T, Miyazaki Y, Ochi F, Akatsuka Y, Okamoto S, Mineno J, Kuzushima K, Ikeda H, Shiku H, Yasukawa M

    Journal of hematology & oncology   Vol. 7   page: 3   2014.1

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/1756-8722-7-3

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  27. An HLA-modified ovarian cancer cell line induced CTL responses specific to an epitope derived from claudin-1 presented by HLA-A*24:02 molecules. Reviewed

    Kondo S, Demachi-Okamura A, Hirosawa T, Maki H, Fujita M, Uemura Y, Akatsuka Y, Yamamoto E, Shibata K, Ino K, Kikkawa F, Kuzushima K

    Human immunology   Vol. 74   page: 1103-1110   2013.9

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.humimm.2013.06.030

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  28. Recognition of a natural WT1 epitope by a modified WT1 peptide-specific T-cell receptor. Reviewed

    Tamanaka T, Oka Y, Fujiki F, Tsuboi A, Katsuhara A, Nakajima H, Hosen N, Nishida S, Lin YH, Tachino S, Akatsuka Y, Kuzushima K, Oji Y, Kumanogoh A, Sugiyama H

    Anticancer research   Vol. 32   page: 5201-5209   2012.12

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    PubMed

  29. Cyclin-A1 represents a new immunogenic targetable antigen expressed in acute myeloid leukemia stem cells with characteristics of a cancer-testis antigen. Reviewed

    Ochsenreither S, Majeti R, Schmitt T, Stirewalt D, Keilholz U, Loeb KR, Wood B, Choi YE, Bleakley M, Warren EH, Hudecek M, Akatsuka Y, Weissman IL, Greenberg PD

    Blood   Vol. 119   page: 5492-5501   2012.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2011-07-365890

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  30. Isolation of human mAbs that directly modulate FMS-related tyrosine kinase 3 signaling. Reviewed

    Yamamoto Y, Tsuzuki S, Akahori Y, Ukai Y, Sumitomo M, Murayama Y, Yamamoto K, Inaguma Y, Tokuda M, Abe A, Akatsuka Y, Emi N, Kurosawa Y

    Cancer science   Vol. 103   page: 350-359   2012.2

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1349-7006.2011.02141.x

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  31. Autophagy creates a CTL epitope that mimics tumor-associated antigens. Reviewed

    Demachi-Okamura A, Torikai H, Akatsuka Y, Miyoshi H, Yoshimori T, Kuzushima K

    PloS one   Vol. 7   page: e47126   2012

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.pone.0047126

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  32. HLA-C matching status does not affect rituximab-mediated antibody-dependent cellular cytotoxicity by allogeneic natural killer Cells. Reviewed

    Machino T, Okoshi Y, Miyake Y, Akatsuka Y, Chiba S

    Immunological investigations   Vol. 41   page: 831-846   2012

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3109/08820139.2012.691148

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  33. Glypican-3 could be an effective target for immunotherapy combined with chemotherapy against ovarian clear cell carcinoma. Reviewed

    Suzuki S, Yoshikawa T, Hirosawa T, Shibata K, Kikkawa F, Akatsuka Y, Nakatsura T

    Cancer science   Vol. 102   page: 1622-1629   2011.9

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1349-7006.2011.02003.x

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  34. Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis. Reviewed

    An J, Fujiwara H, Suemori K, Niiya T, Azuma T, Tanimoto K, Ochi T, Akatsuka Y, Mineno J, Ozawa H, Ishikawa F, Kuzushima K, Yasukawa M

    International journal of hematology   Vol. 93   page: 176-185   2011.2

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-010-0758-7

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  35. The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene. Reviewed

    Isomura H, Stinski MF, Murata T, Nakayama S, Chiba S, Akatsuka Y, Kanda T, Tsurumi T

    PloS one   Vol. 5   page: e11901   2010.7

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.pone.0011901

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  36. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. Reviewed

    Warren EH, Fujii N, Akatsuka Y, Chaney CN, Mito JK, Loeb KR, Gooley TA, Brown ML, Koo KK, Rosinski KV, Ogawa S, Matsubara A, Appelbaum FR, Riddell SR

    Blood   Vol. 115   page: 3869-3878   2010.5

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2009-10-248997

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  37. Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation. Reviewed

    Villalobos IB, Takahashi Y, Akatsuka Y, Muramatsu H, Nishio N, Hama A, Yagasaki H, Saji H, Kato M, Ogawa S, Kojima S

    Blood   Vol. 115 ( 15 ) page: 3158-3161   2010.4

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2009-11-254284

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    J-GLOBAL

  38. Frequent inactivation of A20 in B-cell lymphomas. Reviewed

    Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J, Asakura Y, Muto S, Tamura A, Iio M, Akatsuka Y, Hayashi Y, Mori H, Igarashi T, Kurokawa M, Chiba S, Mori S, Ishikawa Y, Okamoto K, Tobinai K, Nakagama H, Nakahata T, Yoshino T, Kobayashi Y, Ogawa S

    Nature   Vol. 459   page: 712-716   2009.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nature07969

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  39. Exploration of the genetic basis of GVHD by genetic association studies. Reviewed

    Ogawa S, Matsubara A, Onizuka M, Kashiwase K, Sanada M, Kato M, Nannya Y, Akatsuka Y, Satake M, Takita J, Chiba S, Saji H, Maruya E, Inoko H, Morishima Y, Kodera Y, Takehiko S, Japan Marrow Donation Program (JMDP)

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 15   page: 39-41   2009.1

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbmt.2008.11.020

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  40. CD137-guided isolation and expansion of antigen-specific CD8 cells for potential use in adoptive immunotherapy. Reviewed

    Watanabe K, Suzuki S, Kamei M, Toji S, Kawase T, Takahashi T, Kuzushima K, Akatsuka Y

    International journal of hematology   Vol. 88   page: 311-320   2008.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-008-0134-z

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  41. Epstein-Barr virus nuclear antigen 1-specific CD4+ T cells directly kill Epstein-Barr virus-carrying natural killer and T cells. Reviewed

    Demachi-Okamura A, Ito Y, Akatsuka Y, Tsujimura K, Morishima Y, Takahashi T, Kuzushima K

    Cancer science   Vol. 99   page: 1633-1642   2008.8

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1349-7006.2008.00852.x

    PubMed

  42. Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor alpha2 chain, a glioma-associated antigen. Reviewed

    Shimato S, Natsume A, Wakabayashi T, Tsujimura K, Nakahara N, Ishii J, Ito M, Akatsuka Y, Kuzushima K, Yoshida J

    Journal of neurosurgery   Vol. 109   page: 117-122   2008.7

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    DOI: 10.3171/JNS/2008/109/7/0117

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  43. CD16+ CD56- NK cells in the peripheral blood of cord blood transplant recipients: a unique subset of NK cells possibly associated with graft-versus-leukemia effect. Reviewed

    Lu X, Kondo Y, Takamatsu H, Ohata K, Yamazaki H, Takami A, Akatsuka Y, Nakao S

    European journal of haematology   Vol. 81   page: 18-25   2008.7

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1600-0609.2008.01073.x

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  44. Aberrant expression of BCL2A1-restricted minor histocompatibility antigens in melanoma cells: application for allogeneic transplantation. Reviewed

    Torikai H, Akatsuka Y, Yatabe Y, Morishima Y, Kodera Y, Kuzushima K, Takahashi T

    International journal of hematology   Vol. 87   page: 467-473   2008.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-008-0076-5

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  45. DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells. Reviewed

    Rosinski KV, Fujii N, Mito JK, Koo KK, Xuereb SM, Sala-Torra O, Gibbs JS, Radich JP, Akatsuka Y, Van den Eynde BJ, Riddell SR, Warren EH

    Blood   Vol. 111   page: 4817-4826   2008.5

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2007-06-096313

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  46. Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions. Reviewed

    Akatsuka Y, Morishima Y, Kuzushima K, Kodera Y, Takahashi T

    Cancer science   Vol. 98   page: 1139-1146   2007.8

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1349-7006.2007.00521.x

    PubMed

  47. Full-length EBNA1 mRNA-transduced dendritic cells stimulate cytotoxic T lymphocytes recognizing a novel HLA-Cw*0303- and -Cw*0304-restricted epitope on EBNA1-expressing cells. Reviewed

    Ito Y, Demachi-Okamura A, Ohta R, Akatsuka Y, Nishida K, Tsujimura K, Morishima Y, Takahashi T, Kuzushima K

    The Journal of general virology   Vol. 88   page: 770-780   2007.3

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1099/vir.0.82519-0

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  48. Effects of HLA allele and killer immunoglobulin-like receptor ligand matching on clinical outcome in leukemia patients undergoing transplantation with T-cell-replete marrow from an unrelated donor. Reviewed

    Morishima Y, Yabe T, Matsuo K, Kashiwase K, Inoko H, Saji H, Yamamoto K, Maruya E, Akatsuka Y, Onizuka M, Sakamaki H, Sao H, Ogawa S, Kato S, Juji T, Sasazuki T, Kodera Y, Japan Marrow Donor Program

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 13   page: 315-328   2007.3

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbmt.2006.10.027

    PubMed

  49. Identification of an HLA-A24-restricted cytotoxic T lymphocyte epitope from human papillomavirus type-16 E6: the combined effects of bortezomib and interferon-gamma on the presentation of a cryptic epitope. Reviewed

    Morishima S, Akatsuka Y, Nawa A, Kondo E, Kiyono T, Torikai H, Nakanishi T, Ito Y, Tsujimura K, Iwata K, Ito K, Kodera Y, Morishima Y, Kuzushima K, Takahashi T

    International journal of cancer. Journal international du cancer   Vol. 120   page: 594-604   2007.2

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ijc.22312

    PubMed

  50. Bone marrow may be a reservoir of long-lived memory T cells specific for minor histocompatibility antigen. Reviewed

    Akatsuka Y, Torikai H, Inamoto Y, Tsujimura K, Morishima Y, Kodera Y, Kuzushima K, Takahashi T

    British journal of haematology   Vol. 135   page: 413-414   2006.11

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1365-2141.2006.06313.x

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  51. Generation of peptide-specific CD8+ T cells by phytohemagglutinin-stimulated antigen-mRNA-transduced CD4+ T cells. Reviewed

    Naota H, Miyahara Y, Okumura S, Kuzushima K, Akatsuka Y, Hiasa A, Kitano S, Takahashi T, Yuta A, Majima Y, Shiku H

    Journal of immunological methods   Vol. 314   page: 54-66   2006.7

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jim.2006.05.009

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  52. Characterization of murine CD160+ CD8+ T lymphocytes. Reviewed

    Tsujimura K, Obata Y, Matsudaira Y, Nishida K, Akatsuka Y, Ito Y, Demachi-Okamura A, Kuzushima K, Takahashi T

    Immunology letters   Vol. 106   page: 48-56   2006.7

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.imlet.2006.04.006

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  53. Epstein-Barr virus (EBV) latent membrane protein-1-specific cytotoxic T lymphocytes targeting EBV-carrying natural killer cell malignancies. Reviewed

    Demachi-Okamura A, Ito Y, Akatsuka Y, Tsujimura K, Morishima Y, Takahashi T, Kuzushima K

    European journal of immunology   Vol. 36   page: 593-602   2006.3

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/eji.200535485

    PubMed

  54. Three immunoproteasome-associated subunits cooperatively generate a cytotoxic T-lymphocyte epitope of Epstein-Barr virus LMP2A by overcoming specific structures resistant to epitope liberation. Reviewed

    Ito Y, Kondo E, Demachi-Okamura A, Akatsuka Y, Tsujimura K, Tanimoto M, Morishima Y, Takahashi T, Kuzushima K

    Journal of virology   Vol. 80   page: 883-890   2006.1

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/JVI.80.2.883-890.2006

    PubMed

  55. A UGT2B17-positive donor is a risk factor for higher transplant-related mortality and lower survival after bone marrow transplantation. Reviewed

    Terakura S, Murata M, Nishida T, Emi N, Akatsuka Y, Riddell SR, Morishima Y, Kodera Y, Naoe T

    British journal of haematology   Vol. 129   page: 221-228   2005.4

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1365-2141.2005.05427.x

    PubMed

  56. Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases). Reviewed

    Storek J, Zhao Z, Lin E, Berger T, McSweeney PA, Nash RA, Akatsuka Y, Metcalf MD, Lu H, Kalina T, Reindl M, Storb R, Hansen JA, Sullivan KM, Kraft GH, Furst DE, Maloney DG

    Clinical immunology (Orlando, Fla.)   Vol. 113   page: 285-298   2004.12

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.clim.2004.07.006

    PubMed

  57. The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma. Reviewed

    Ishida T, Iida S, Akatsuka Y, Ishii T, Miyazaki M, Komatsu H, Inagaki H, Okada N, Fujita T, Shitara K, Akinaga S, Takahashi T, Utsunomiya A, Ueda R

    Clinical cancer research : an official journal of the American Association for Cancer Research   Vol. 10   page: 7529-7539   2004.11

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1158/1078-0432.CCR-04-0983

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  58. Immunity against mouse thymus-leukemia antigen (TL) protects against development of lymphomas induced by a chemical carcinogen, N-butyl-N-nitrosourea. Reviewed

    Tsujimura K, Obata Y, Matsudaira Y, Ozeki S, Taguchi O, Nishida K, Okanami Y, Akatsuka Y, Kuzushima K, Takahashi T

    Cancer science   Vol. 95   page: 914-919   2004.11

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1349-7006.2004.tb02202.x

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  59. Interferon-gamma differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes. Reviewed

    Tajima K, Ito Y, Demachi A, Nishida K, Akatsuka Y, Tsujimura K, Hida T, Morishima Y, Kuwano H, Mitsudomi T, Takahashi T, Kuzushima K

    International journal of cancer. Journal international du cancer   Vol. 110   page: 403-412   2004.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ijc.20139

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  60. Clinical relevance of a newly identified HLA-A24-restricted minor histocompatibility antigen epitope derived from BCL2A1, ACC-1, in patients receiving HLA genotypically matched unrelated bone marrow transplant. Reviewed

    Nishida T, Akatsuka Y, Morishima Y, Hamajima N, Tsujimura K, Kuzushima K, Kodera Y, Takahashi T

    British journal of haematology   Vol. 124   page: 629-635   2004.3

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1365-2141.2004.04823.x

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  61. Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles. Reviewed

    Kondo E, Akatsuka Y, Kuzushima K, Tsujimura K, Asakura S, Tajima K, Kagami Y, Kodera Y, Tanimoto M, Morishima Y, Takahashi T

    Blood   Vol. 103   page: 630-638   2004.1

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2003-03-0824

    PubMed

  62. Disparity for a newly identified minor histocompatibility antigen, HA-8, correlates with acute graft-versus-host disease after haematopoietic stem cell transplantation from an HLA-identical sibling. Reviewed

    Akatsuka Y, Warren EH, Gooley TA, Brickner AG, Lin MT, Hansen JA, Martin PJ, Madtes DK, Engelhard VH, Takahashi T, Riddell SR

    British journal of haematology   Vol. 123   page: 671-675   2003.11

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1046/j.1365-2141.2003.04676.x

    PubMed

  63. Thymus leukemia antigen (TL)-specific cytotoxic T lymphocytes recognize the alpha1/alpha2 domain of TL free from antigenic peptides. Reviewed

    Tsujimura K, Obata Y, Kondo E, Nishida K, Matsudaira Y, Akatsuka Y, Kuzushima K, Takahashi T

    International immunology   Vol. 15   page: 1319-1326   2003.11

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/intimm/dxg131

    PubMed

  64. Restoration of CD28 expression in CD28- CD8+ memory effector T cells reconstitutes antigen-induced IL-2 production. Reviewed

    Topp MS, Riddell SR, Akatsuka Y, Jensen MC, Blattman JN, Greenberg PD

    The Journal of experimental medicine   Vol. 198   page: 947-955   2003.9

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20021288

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  65. Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells. Reviewed

    Miyazaki M, Akatsuka Y, Nishida T, Fujii N, Hiraki A, Ikeda K, Tsujimura K, Kuzushima K, Morishima Y, Sato S, Ueda R, Takahashi T

    Clinical immunology (Orlando, Fla.)   Vol. 107   page: 198-201   2003.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/S1521-6616(03)00065-2

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  66. Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens. Reviewed

    Akatsuka Y, Nishida T, Kondo E, Miyazaki M, Taji H, Iida H, Tsujimura K, Yazaki M, Naoe T, Morishima Y, Kodera Y, Kuzushima K, Takahashi T

    The Journal of experimental medicine   Vol. 197   page: 1489-1500   2003.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20021925

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  67. Tetramer-assisted identification and characterization of epitopes recognized by HLA A*2402-restricted Epstein-Barr virus-specific CD8+ T cells. Reviewed

    Kuzushima K, Hayashi N, Kudoh A, Akatsuka Y, Tsujimura K, Morishima Y, Tsurumi T

    Blood   Vol. 101   page: 1460-1468   2003.2

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2002-04-1240

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  68. Targeted cloning of cytotoxic T cells specific for minor histocompatibility antigens restricted by HLA class I molecules of interest. Reviewed

    Akatsuka Y, Kondo E, Taji H, Morishima Y, Yazaki M, Obata Y, Kodera Y, Riddell SR, Takahashi T

    Transplantation   Vol. 74   page: 1773-1780   2002.12

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1097/01.TP.0000039166.86548.93

    PubMed

  69. Association between immune recovery uveitis and a diverse intraocular cytomegalovirus-specific cytotoxic T cell response. Reviewed

    Mutimer HP, Akatsuka Y, Manley T, Chuang EL, Boeckh M, Harrington R, Jones T, Riddell SR

    The Journal of infectious diseases   Vol. 186   page: 701-705   2002.9

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1086/342044

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  70. Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells. Reviewed

    Kondo E, Topp MS, Kiem HP, Obata Y, Morishima Y, Kuzushima K, Tanimoto M, Harada M, Takahashi T, Akatsuka Y

    Journal of immunology (Baltimore, Md. : 1950)   Vol. 169   page: 2164-2171   2002.8

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    PubMed

  71. Determination of intronic sequences adjacent to an exon using polymerase chain reaction and genomic DNA library constructed by TA cloning. Reviewed

    Akatsuka Y, Warren EH, Brickner AG, Engelhard VH, Riddell SR

    Analytical biochemistry   Vol. 289   page: 289-292   2001.2

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1006/abio.2000.4897

    PubMed

  72. Generation of HLA-C-specific cytotoxic T cells in association with marrow graft rejection: analysis of alloimmunity by T-cell cloning and testing of T-cell-receptor rearrangements. Reviewed

    Pei J, Akatsuka Y, Anasetti C, Lin MT, Petersdorf EW, Hansen JA, Martin PJ

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation   Vol. 7   page: 378-383   2001

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    Publishing type:Research paper (scientific journal)  

    PubMed

  73. Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. Reviewed

    Lin MT, Tseng LH, Frangoul H, Gooley T, Pei J, Barsoukov A, Akatsuka Y, Hansen JA

    Blood   Vol. 95   page: 3832-3839   2000.6

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    Publishing type:Research paper (scientific journal)  

    PubMed

  74. Immunotherapy of human viral and malignant diseases with genetically modified T-cell clones. Reviewed

    Riddell SR, Warren EH, Gavin MA, Akatsuka Y, Lewinsohn D, Mutimer H, Cooper L, Topp MS, Bonini C, Greenberg PD

    Cancer journal (Sudbury, Mass.)   Vol. 6 Suppl 3   page: S250-8   2000.5

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    Publishing type:Research paper (scientific journal)  

    PubMed

  75. A novel minor histocompatibility antigen recognized by HLA-A31 restricted cytotoxic T lymphocytes generated from HLA-identical bone marrow donor lymphocytes. Reviewed

    Yazaki M, Takahashi T, Andho M, Akatsuka Y, Ito T, Miyake Y, Ito Y, Nakamura S, Wada Y

    Bone marrow transplantation   Vol. 24   page: 129-137   1999.7

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/sj.bmt.1701856

    PubMed

  76. Role of mitogen-activated protein kinases in activation-induced apoptosis of T cells. Reviewed

    Zhu L, Yu X, Akatsuka Y, Cooper JA, Anasetti C

    Immunology   Vol. 97   page: 26-35   1999.5

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1046/j.1365-2567.1999.00756.x

    PubMed

  77. Rapid screening of T-cell receptor (TCR) variable gene usage by multiplex PCR: application for assessment of clonal composition. Reviewed

    Akatsuka Y, Martin EG, Madonik A, Barsoukov AA, Hansen JA

    Tissue antigens   Vol. 53   page: 122-134   1999.2

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1034/j.1399-0039.1999.530202.x

    PubMed

  78. Immune response of post-transplant peripheral lymphocytes against the patient pre-B cell line, NAGL-1. Reviewed

    Kasai M, Akatsuka Y, Emi N, Taji H, Kohno A, Abe A, Tanimoto M, Kodera Y, Saito H

    International journal of hematology   Vol. 69 ( 2 ) page: 112-118   1999.2

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    Publishing type:Research paper (scientific journal)  

    PubMed

  79. Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow graft rejection. Reviewed

    Martin PJ, Akatsuka Y, Hahne M, Sale G

    Blood   Vol. 92 ( 6 ) page: 2177-2181   1998.9

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    Publishing type:Research paper (scientific journal)  

    PubMed

  80. Prolonged selective neutropenia after allogeneic bone marrow transplantation: possible effect of presensitization by donor lymphocytes prior to transplant. Reviewed

    Towatari M, Miyamura K, Akatsuka Y, Yamamoto K, Minami S, Kodera Y

    International journal of hematology   Vol. 66 ( 4 ) page: 513-516   1997.12

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/S0925-5710(97)00071-6

    PubMed

    CiNii Article

    J-GLOBAL

  81. T cell receptor clonal diversity following allogeneic marrow grafting. Reviewed

    Akatsuka Y, Cerveny C, Hansen JA

    Human immunology   Vol. 48 ( 1/2 ) page: 125-134   1996.6

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/0198-8859(96)00082-1

    PubMed

    CiNii Article

    J-GLOBAL

  82. Retrovirus-mediated transfer of a hygromycin phosphotransferase-thymidine kinase fusion gene into human CD34+ bone marrow cells. Reviewed

    Akatsuka Y, Emi N, Kato H, Abe A, Tanimoto M, Lupton SD, Saito H

    International journal of hematology   Vol. 60 ( 4 ) page: 251-261   1994.12

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    Publishing type:Research paper (scientific journal)  

    PubMed

  83. Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia. Reviewed

    Kubo K, Naoe T, Kiyoi H, Fukutani H, Kato Y, Oguri T, Yamamori S, Akatsuka Y, Kodera Y, Ohno R

    Japanese journal of cancer research : Gann   Vol. 84 ( 4 ) page: 379-387   1993.4

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    Publishing type:Research paper (scientific journal)  

    PubMed

  84. Acute renal failure and degenerative tubular lesions associated with in situ formation of adenovirus immune complexes in a patient with allogeneic bone marrow transplantation. Reviewed

    Yuzawa Y, Aoi N, Fukatsu A, Ichida S, Yoshida F, Akatsuka Y, Minami S, Kodera Y, Matsuo S

    Transplantation   Vol. 55 ( 1 ) page: 67-72   1993.1

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    Publishing type:Research paper (scientific journal)  

    PubMed

  85. Bone marrow transplantation for chronic myelogenous leukemia in blastic phase using a phenotypically identical unrelated volunteer donor. Nagoya Bone Marrow Transplantation Group (NBMTG), Tokai Marrow Donor Bank (TMDB). Reviewed

    Akatsuka Y, Kodera Y, Yamamoto K, Minami S, Miyamura K, Morishita Y, Morishima Y, Saitoh H, Horibe K, Yamauchi T

    International journal of hematology   Vol. 55 ( 3 ) page: 249-253   1992.6

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    Publishing type:Research paper (scientific journal)  

    PubMed

  86. Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation. Reviewed

    Miyamura K, Tanimoto M, Morishima Y, Horibe K, Yamamoto K, Akatsuka M, Kodera Y, Kojima S, Matsuyama K, Hirabayashi N

    Blood   Vol. 79   page: 1366-1370   1992.3

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    Publishing type:Research paper (scientific journal)  

    PubMed

  87. Changes of an androgen-dependent nuclear protein during functional differentiation and by dedifferentiation of the dorsolateral prostate of rats. Reviewed

    Matuo Y, Nishi N, Tanaka Y, Muguruma Y, Tanaka K, Akatsuka Y, Matsui SI, Sandberg AA, Wada F

    Biochemical and biophysical research communications   Vol. 118 ( 2 ) page: 467-473   1984.1

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/0006-291X(84)91326-3

    PubMed

    CiNii Article

    J-GLOBAL

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Books 2

  1. 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

  2. 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 16

  1. がん免疫療法の展開と展望 Invited

    赤塚 美樹

    現代医学   Vol. 67 ( 2 ) page: 37 - 46   2020.12

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

  2. RINKETSU Dictionary 免疫抑制性細胞 Invited

    赤塚美樹

    臨床血液   Vol. 61 ( 7 ) page: 843 - 843   2020.7

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    Authorship:Lead author   Language:Japanese  

  3. CAR-T細胞療法の基礎と今後の臨床展開 Invited Reviewed

    赤塚 美樹

    日本輸血細胞治療学会誌   Vol. 65 ( 6 ) page: 851 - 857   2019.12

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:(一社)日本輸血・細胞治療学会  

    キメラ抗原受容体(Chimeric Antigen Receptor、CAR)-T細胞療法は遺伝子改変T細胞による養子免疫療法の一つであり、急性リンパ性白血病、悪性リンパ腫、慢性リンパ性白血病などのB細胞性腫瘍や多発性骨髄腫に対する新規治療法として近年非常に注目されている。CD19抗原を標的としたCAR-T細胞による国際共同第2相試験において、難治性B細胞性腫瘍に対して高率な寛解導入効果が示された。CAR-T細胞は短期間で調製でき、T細胞が持つT細胞受容体より高い親和性をもった抗体を抗原受容体として利用したことが成功に寄与した。また抗体を抗原受容体とすることでT細胞のHLA拘束性を考慮する必要がない。CARの構造は細胞外ドメインとし抗体のFab部分と、細胞内ドメインとしてT細胞のシグナルドメインから成る。T細胞の活性化や機能増強、体内での長期生存能を付与するために細胞内ドメインにはさまざまな工夫が施されてきた。ただし治療後にサイトカイン放出症候群などの重篤な副作用が高頻度に起こりうる他、長期的には一部に再発も認められ、今後解決すべき課題も残されている。(著者抄録)

  4. 【細胞治療の新時代】T細胞受容体導入T細胞 Invited

    赤塚 美樹

    日本内科学会雑誌   Vol. 108 ( 7 ) page: 1384 - 1390   2019.7

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  5. 樹状細胞ワクチンによるWT-1を標的とするCAR-T細胞による抗腫瘍効果の増強 International journal

    赤堀 泰, 藤原 弘, 王 立楠, 米山 元裕, 瀬尾 尚宏, 奥村 悟司, 宮原 慶裕, 池田 裕明, 天石 泰典, 岡本 幸子, 峰野 純一, 真木 健裕, 赤塚 美樹, 加藤 琢磨, 珠玖 洋

    血液内科   Vol. 78 ( 5 ) page: 696 - 701   2019.5

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    Language:Japanese   Publisher:(有)科学評論社  

  6. がん免疫成立の基盤となるCancer-Immunity Cycle Invited

    赤塚美樹, 西川博嘉

    TRENDS IN CANCER IMMUNOLOGY   Vol. - ( - ) page: 2 - 5   2018.12

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

  7. WT1を標的としたCAR治療法についてのワクチン活性化作用の検討(Anti-tumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination)

    赤堀 泰, 王 立楠, 米山 元裕, 瀬尾 尚宏, 赤塚 美樹, 加藤 琢磨, 天石 泰典, 岡本 幸子, 峯野 純一, 池田 裕明, 真木 健裕, 藤原 弘, 珠玖 洋

    日本癌学会総会記事   Vol. 77回   page: 1231 - 1231   2018.9

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    Language:English   Publishing type:Meeting report   Publisher:日本癌学会  

  8. ヒト培養細胞を用いたTCR親和性成熟システムの樹立

    太田 里永子, 岡村 文子, 赤塚 美樹, 葛島 清隆

    日本がん免疫学会総会プログラム・抄録集   Vol. 22回   page: 127 - 127   2018.7

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    Language:Japanese   Publishing type:Meeting report   Publisher:日本がん免疫学会  

  9. Historical perspectives and future directions of gene-modified T-cell therapy. Reviewed

    Akatsuka Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 57 ( 10 ) page: 2241-2249   2016

  10. [Frequent inactivation of A20 through gene mutation in B-cell lymphomas]. Reviewed

    Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J, Asakura Y, Akatsuka M, Hayashi Y, Mori H, Igarashi T, Kurokawa M, Chiba S, Mori S, Ishikawa Y, Okamoto K, Tobinai K, Nakagama H, Nakahata T, Yoshino T, Kobayashi Y, Ogawa S

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 52   page: 313-319   2011.6

  11. [Possibility of selective induction of a GVL effect without increasing GVHD]. Reviewed

    Akatsuka Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 49 ( 8 ) page: 607-615   2008.8

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  12. [Antigen-specific allogeneic immunotherapy--selective augmentation of GVL effects]. Reviewed

    Akatsuka Y

    Gan to kagaku ryoho. Cancer & chemotherapy   Vol. 35 ( 5 ) page: 713-719   2008.5

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  13. [Principal and perspective of adoptive immuno-cell therapy for hematological malignancies]. Reviewed

    Akatsuka Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 48 ( 10 ) page: 1328-1338   2007.10

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  14. [Role of minor histocompatibility antigens in hematopoietic cell transplantation]. Reviewed

    Akatsuka Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 47 ( 10 ) page: 1353-1363   2006.10

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  15. [Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank]. Reviewed

    Matsumoto K, Horibe K, Akatsuka Y, Minami S, Matsuyama T, Hirabayashi N, Tanimoto M, Yamada H, Sobue R, Morishima Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 35   page: 729-737   1994.8

  16. [Allogeneic cryopreserved marrow transplantation in a patient with chronic myelogenous leukemia]. Reviewed

    Akatsuka Y, Takeshita T, Tsuzuki S, Suzuki R, Sugihara T, Minami S, Kodera Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   Vol. 35   page: 304-308   1994.3

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Presentations 87

  1. HLA-A2に提示されたマイナー抗原HA-1認識抗体の開発と応用(Construction and molecular characterization of a single chain antibody specific for HA-1 minor H antigen)

    赤塚 美樹, 岡村 文子, 山本 幸也, 西村 泰治, 高橋 利忠, 葛島 清隆, 恵美 宣彦

    日本癌学会総会記事  2013.10  日本癌学会

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    Event date: 2013.10

    Language:Japanese   Presentation type:Oral presentation (general)  

  2. HLA-A2拘束性に提示されたマイナー抗原HA-1Hを認識する抗体の単離とCAR-Tの機能

    赤塚 美樹, 赤堀 泰, 稲熊 容子, 村山 裕子, 辻川 朱里, 平松 可帆, 西村 泰治, 葛島 清隆, 恵美 宣彦

    日本がん免疫学会総会プログラム・抄録集  2013.7  日本がん免疫学会

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    Event date: 2013.7

    Language:Japanese   Presentation type:Oral presentation (general)  

  3. Alternative Splicing Due to an Intronic SNP Defines a Novel HLA-B44-Restricted-Hematopoiesis-Restricted Minor Histocompatibility Antigen. International conference

    Takakazu Kawase, Yoshiki Akatsuka, Hiroki Torikai, Satoko Morishima, Yoshihisa Kodera, Yasuo Morishima, Kiyotaka Kuzushima, Toshitada Takahashi

    Blood  2006.11.16  American Society of Hematology

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    Event date: 2006.11

    Language:English   Presentation type:Poster presentation  

    <title>Abstract</title>
    Minor histocompatibility antigens (mHAgs) with expression limited to hematopoietic cells represent attractive targets for immunotherapy to induce selective graft-versus-leukemia (GVL) reactions. Here we report the identification of a novel mHAg which is recognized by an HLA-B*4403-restricted CTL clone. Microsatellite allele image analysis of two DNA pools generated from CTL-defined mHAg positive and mHAg negative groups was performed using microsatellite markers set at 100 kb intervals within the segment initially mapped by two-point genetic linkage analysis and detailed mapping of the chromosomal recombinant points. This approach defined a 0.53 Mbp region of chromosome 18q21–22 containing 12 candidate genes potentially encoding the mHAg, although the target gene could not be identified. Subsequently, cDNA expression cloning studies demonstrated that the CTL epitope of interest was encoded by a novel allelic splice variant of XM_209104, hereafter designated as XM_209104-av. Indeed, this gene was found to lie within the region predicted by microsatellite allele image analysis. The immunogenicity of the epitope was generated by differential protein expression due to alternative splicing, which was completely controlled by one intronic single nucleotide polymorphism (SNP) located in the consensus 5′ splice site adjacent to an exon. To our knowledge, this is the first example of a mHAg controlled by a SNP located in a region other than coding sequences. Because the CTL lysed also HLA-B*4402 positive, mHAg positive B-LCLs, this novel epitope peptide can bind to not only HLA-B*4403 but also HLA-B*4402 which is a relatively common HLA-B allele in Caucasian populations. Finally, the finding that the novel XM_209104-av showed low or no expression in normal tissues including resting hematopoietic cells, but significantly higher expression in primary acute leukemia cells, especially those of myeloid lineage, suggest that this novel epitope may be an attractive therapeutic target for immunotherapy not only as a minor H antigen but also as a leukemia-associated antigen.

  4. 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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    Presentation type:Oral presentation (invited, special)  

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

  6. 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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  7. Identification of T-Cell Receptors Specific to Antigens Presented By HLA-B4002 and B5401 in Acquired Aplastic Anemia International conference

    Kohei Hosokawa, Eiji Kobayashi, Yoshiki Akatsuka, Luis Espinoza, Noriharu Nakagawa, Tanabe Mikoto, Noriaki Tsuji, Takeshi Yoroidaka, Hiroki Mizumaki, Thi Mai Anh Nguyen, Takamasa Katagiri, Kiyomi Shitaoka, Hiroshi Hamana, Hiroyuki Kishi, Shinji Nakao

    Blood  2019.11.13  American Society of Hematology

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    Event date: 2019.11

    Language:English   Presentation type:Oral presentation (general)  

    [Background] Leukocytes that lack HLA class I alleles derived from hematopoietic stem progenitor cells (HSPCs) that undergo copy number neutral loss of heterozygosity of the short arm of chromosome 6 (6pLOH) or HLA allelic mutations are often detected in acquired aplastic anemia (AA) patients. The presence of HLA class I allele-lacking leukocytes provides compelling evidence that cytotoxic T lymphocytes (CTLs) are involved in the development of AA. Our recent study showed that, among several HLA-class I alleles that are likely to be lost as a result of 6pLOH, HLA-B*40:02 is the most frequently lost allele in AA. Therefore, HLA-B*4002 is thought to play a critical role in the autoantigen presentation by HSPCs to CTLs. We previously identified the T-cell receptor (TCR) sequences from bone marrow (BM) CD8+ T cells in two CsA-dependent AA patients possessing B4002-lacking leukocytes (Case 1, Espinoza et al, Blood Adv, 2018) and B5401-lacking leukocytes (Case 2, Elbadry et al, Haematologica, 2019) by single-cell T-cell receptor (TCR) sequencing. Identifying the TCRs specific to antigens presented by these HLA class I alleles should allow us to screen autoantigens in AA. [Method] We established B4002+ or B5401+ K562 cell lines expressing CD80 and CD137L for the screening of antigen-specific T cell responses. To identify ligands of the TCR, we transfected peripheral blood (PB) T cells with a retrovirus vector containing different TCR cDNA derived from BM T cells and examined their responses to B4002+CD80+CD137L+ or B5401+CD80+CD137L+ K562 cells. Specific responses of each TCR transfectant to K562 cells or iPSC-derived CD34+ cells were determined using an enzyme-linked immunosorbent assay for detecting IFN-γ. Deep TCR sequencing of a current PB sample taken from the same patients was performed to determine whether or not T cells with specific TCRs persisted after successful immunosuppressive therapy (IST). [Results] In Case 1, two TCR transfectants (TCR-K1 and TCR-K2 which were the third- and second-most frequent TCRs in the BM T cells, respectively) secreted greater IFN-γ levels (1730 pg/mL and 2157 pg/mL, respectively) in response to B4002+CD80+CD137L+ K562 cells than those secreted by the other six transfectants (710 to 1184 pg/mL, respectively). TCR-K1 and TCR-K2 did not respond to an A2402+ counterpart (Figure). Notably, deep TCR sequencing of a current PB sample taken from Case 1 nine years after BM sampling revealed the persistence of the TCR-K1 sequence, suggesting that TCR-K1 may be responsible for CsA dependency of this patient. Deep TCR sequencing of other three AA patients with B4002-lacking leukocytes revealed decreased diversity of the T cell repertoire in CD8+ T cells but failed to reveal the same TCR motifs as Case 1. In Case 2, two TCR transfectants (TCR-K3 and TCR-K4) showed a specific response to B5401+CD80+CD137L+ K562 cells. Furthermore, these 2 TCR transfectants secreted higher amounts of IFN-γ (1.7 and 2.0 folds for TCR-K3 and TCR-K4, respectively) in response to wild-type iPSC-derived CD34+ cells than to B5401(-) CD34+ cells. [Conclusions] Our results suggest that these TCR transfectants recognized some intrinsic antigens derived from K562 cells in a B4002 or B5401-restricted manner. These TCR transfectants are the ideal tools for screening libraries of cDNA expressed by B4002+ COS/293T cells to identify autoantigens in AA.


    Figure


    <sec>
    <title>Disclosures</title>
    Yoroidaka: Ono Pharmaceutical: Honoraria. Nakao:Takeda Pharmaceutical Company Limited: Honoraria; Bristol-Myers Squibb: Honoraria; Alaxion Pharmaceuticals: Honoraria; Ohtsuka Pharmaceutical: Honoraria; Daiichi-Sankyo Company, Limited: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; SynBio Pharmaceuticals: Consultancy; Chugai Pharmaceutical Co.,Ltd: Honoraria; Ono Pharmaceutical: Honoraria; Celgene: Honoraria; Kyowa Kirin: Honoraria; Novartis Pharma K.K: Honoraria.


    </sec>

  8. 健常人における試験管法とカラム遠心凝集法の抗A/B抗体価測定の比較検討

    松浦 秀哲, 赤塚 美樹, 松野 貴洋, 杉浦 縁, 荒川 章子, 及川 彰太, 吉田 純平, 古杉 光明, 恵美 宣彦

    日本輸血細胞治療学会誌  2019.6  (一社)日本輸血・細胞治療学会

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    Event date: 2019.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    移植前後における抗A/B抗体価を測定することは治療選択に有用である。現在、抗体価測定法は試験管法が推奨されており、Dithiothreitol(DTT)は試験管法の抗体価測定においてIgMを不活化するために使用されている。最近、カラム遠心凝集法を原理とした全自動で抗体価を測定できる装置(auto-CAT)が開発され、1)抗A/B抗体価測定において試験管法とauto-CATを比較すること、2)auto-CATにおけるDTT処理の影響を評価すること、3)auto-CATにおける抗体価測定のカットオフ値を決定することを目的に本検討を実施した。我々は、A型10名、B型10名、O型10名の合計30名の健常ボランティアを対象とした。対象から得た血液サンプルを用い、同時に試験管法とauto-CATで抗体価を測定した。全症例を対象にした場合、auto-CATはDTT処理血漿を用い、カットオフ値をw+に設定すると、試験管法との一致率は45%、重み付けκ係数は0.994となった。さらに、試験管法とauto-CATで測定した抗A/B抗体価の間には有意な正の相関関係を認めた。また、auto-CATにおいてDTT処理に起因する偽陽性反応は認めなかった。試験管法で使用しているカットオフ値1+は、auto-CATではw+に相当する。本検討はDTT処理を行い、カットオフ値をw+にしたauto-CATにおける抗体価の結果が標準法である試験管法の結果と一致性が高まることを示した。我々は、auto-CATによる抗体価測定が日常検査に有用であると考える。(著者抄録)

  9. ETV6の再構成による異所性遺伝子発現を認めた急性骨髄性白血病の二症例(Two cases of AML with ectopic gene expression resulting from the ETV6 rearrangements)

    安部 明弘, 山本 幸也, 岡本 晃直, 入山 智沙子, 徳田 倍将, 稲熊 容子, 蟹江 匡治, 冨田 章裕, 赤塚 美樹, 岡本 昌隆, 亀山 俊樹, 前田 明, 恵美 宣彦

    臨床血液  2018.9  (一社)日本血液学会-東京事務局

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    Event date: 2018.9

  10. 消化管出血時の緊急輸血にて、アナフィラキシー・ショックを合併したIgA欠損症の1例

    岡本 晃直, 村松 知佳, 坂本 悠斗, 永田 梨奈, 及川 彰太, 松野 貴洋, 西垣 亮, 磯貝 聡衣, 加藤 友理, 松浦 秀哲, 柴田 亜委, 荒川 章子, 杉浦 縁, 恵美 宣彦, 赤塚 美樹

    日本輸血細胞治療学会誌  2018.6  (一社)日本輸血・細胞治療学会

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    Event date: 2018.6

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

  11. D抗原に特異性を持つ抗体を保有するRhD陽性の2症例

    坂本 悠斗, 松浦 秀哲, 杉浦 縁, 林 由芽, 中村 真理, 松野 貴洋, 永田 梨奈, 及川 彰太, 西垣 亮, 磯貝 聡衣, 村松 知佳, 太田 貴江, 荒川 章子, 赤塚 美樹

    日本輸血細胞治療学会誌  2018.6  (一社)日本輸血・細胞治療学会

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    Event date: 2018.6

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

  12. びまん性大細胞性B細胞リンパ腫における腫瘍浸潤effector regulatory T cell

    河野奨, 河野奨, 島田和之, 赤塚美樹, 赤塚美樹, 鬼頭邦吉, 杉山大介, 伊藤佐知子, 清井仁, 西川博嘉, 中村栄男

    日本リンパ網内系学会会誌  2018.5.31  (一社)日本リンパ網内系学会

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    Event date: 2018.5

    Language:Japanese   Presentation type:Oral presentation (general)  

  13. CD5陽性骨髄原発DLBCL5例の検討

    岡本 晃直, 岡本 昌隆, 岡村 容子, 徳田 倍将, 蟹江 匡治, 山本 幸也, 冨田 章裕, 赤塚 美樹, 恵美 宜彦

    日本リンパ網内系学会会誌  2018.5  (一社)日本リンパ網内系学会

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    Event date: 2018.5

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

  14. 緊急輸血におけるシミュレーション-輸血医療チームの創り方- 輸血医療チームの創り方

    松浦 秀哲, 松野 貴洋, 西垣 亮, 及川 彰太, 林 由芽, 杉浦 縁, 赤塚 美樹

    日本輸血細胞治療学会誌  2018.4  (一社)日本輸血・細胞治療学会

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    Event date: 2018.4

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

  15. 愛知県の12基幹病院における輸血医療のインシデント・アクシデントに関する実態調査

    永田 梨奈, 松浦 秀哲, 杉浦 縁, 石田 高司, 大西 一功, 小澤 幸泰, 笠井 雅信, 加藤 栄史, 木下 朝博, 河野 彰夫, 近藤 勝, 齋藤 俊樹, 澤 正史, 杉浦 勇, 松下 正, 赤塚 美樹, 愛知県合同輸血療法委員会

    日本輸血細胞治療学会誌  2018.4  (一社)日本輸血・細胞治療学会

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    Event date: 2018.4

    Language:Japanese   Presentation type:Oral presentation (general)  

  16. 交差適合試験の省略と簡略化を考える 安全性を重視した高感度交差適合試験の運用

    松浦 秀哲, 杉浦 縁, 荒川 章子, 赤塚 美樹

    日本輸血細胞治療学会誌  2018.4  (一社)日本輸血・細胞治療学会

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    Event date: 2018.4

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

  17. 再発急性骨髄性白血病において微小転座から複数のスプライシング産物を認めたRUNX1-GRIK2融合遺伝子(Multiple splicing transcripts from RUNX1-GRIK2 fusion in a cryptic translocation in a relapsed AML)

    Abe Akihiro, Yamamoto Yukiya, Okamoto Akinao, Tokuda Masutaka, Inaguma Yoko, Yanada Masamitsu, Kanie Tadaharu, Tomita Akihiro, Akatsuka Yoshiki, Okamoto Masataka, Kameyama Toshiki, Maeda Akira, Emi Nobuhiko

    臨床血液  2017.9  (一社)日本血液学会-東京事務局

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    Event date: 2017.9

    Language:English   Presentation type:Oral presentation (general)  

  18. Rasburicase投与後の抗体産生の頻度と抗体価の推移に関する研究

    安藤 舞子, 赤塚 美樹, 伊藤 佳織, 徳田 倍将, 稲熊 容子, 岡本 晃直, 蟹江 匡治, 柳田 正光, 山本 幸也, 冨田 章裕, 岡本 昌隆, 山田 成樹, 恵美 宣彦

    臨床血液  2017.9  (一社)日本血液学会-東京事務局

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    Event date: 2017.9

    Language:Japanese   Presentation type:Poster presentation  

  19. 初発皮下脂肪織炎様T細胞リンパ腫(SPTCL)に対するPSL単剤治療の有効性

    加古 寿志, 岡本 晃直, 冨田 章裕, 稲熊 容子, 徳田 倍将, 蟹江 匡治, 柳田 正光, 山本 幸也, 赤塚 美樹, 岡本 昌隆, 恵美 宣彦

    臨床血液  2017.6  (一社)日本血液学会-東京事務局

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    Event date: 2017.6

    Language:Japanese  

  20. 健常者におけるカラム凝集法と試験管法の抗体価測定の差異の検討

    杉浦 縁, 赤塚 美樹, 松浦 秀哲, 松野 貴洋, 荒川 章子, 及川 彰太, 永田 梨奈, 磯貝 聡衣, 村松 知佳, 柴田 亜委, 岡本 晃直, 恵美 宣彦

    日本輸血細胞治療学会誌  2017.6  (一社)日本輸血・細胞治療学会

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    Event date: 2017.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  21. 当院におけるカリウム吸着フィルターの使用状況

    磯貝 聡衣, 松浦 秀哲, 杉浦 縁, 坂本 悠斗, 永田 梨奈, 及川 彰太, 松野 貴洋, 西垣 亮, 加藤 友理, 村松 知佳, 柴田 亜委, 荒川 章子, 岡本 晃直, 恵美 宣彦, 赤塚 美樹

    日本輸血細胞治療学会誌  2017.4  (一社)日本輸血・細胞治療学会

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    Event date: 2017.4

    Language:Japanese  

  22. Phase 1 Clinical Trial of Adoptive Immunotherapy for Acute Myelogenous Leukemia and Myelodysplastic Syndrome, Using Gene-Modified Autologous Lymphocytes Expressing WT1-Specific T-Cell Receptor International conference

    Kazushi Tanimoto, Hiroshi Fujiwara, Isao Tawara, Masahiro Masuya, Shinichi Kageyama, Tetsuya Nishida, Makoto Murata, Seitaro Terakura, Yoshiki Akatsuka, Hiroaki Ikeda, Yoshihiro Miyahara, Ikuei Nukaya, Kazutoh Takesako, Nobuhiko Emi, Naoyuki Katayama, Hiroshi Shiku, Masaki Yasukawa

    Blood  2016.12.2  American Society of Hematology

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    Event date: 2016.12

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

    <title>Abstract</title>
    Elderly patients (pts) with acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS) particularly who are ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and have disease relapse after allo-HSCT still have a poor prognosis. Thus, the development of novel treatment option providing higher response rate and prolonged survival time for those patients still remains an unmet need. Because not a few clinical and preclinical studies have described a promising value of Wilms Tumor 1 (WT1), a leukemia-associated antigen as a therapeutic target of antileukemia immunotherapy, we conducted a clinical study of novel adoptive immunotherapy using gene-modified autologous lymphocytes expressing WT1-specific T-cell receptor (TCR) for the treatment of refractory AML and high-risk MDS.


    A multicenter phase 1 study was conducted to assess feasibility, safety and preliminary antileukemia reactivity of patient-derived gene-modified lymphocytes expressing WT1-specific TCR. Antigen-specific TCR-gene transfer may cause a serious autoimmune disease mediated by mispaired TCR between introduced and endogenous TCR α/β chains. To avoid that, we established a retroviral vector system encoding siRNAs for endogenous TCR genes (siTCR vector). We conducted a first-in-human clinical trial employing this siTCR vector. After given written informed consents, mononuclear cells were collected from at most 200ml of peripheral blood (PB) from each patient. Then, proliferating lymphocytes pre-cultured with IL-2, anti-CD3 antibody and RetroNectinTM were infected with a retroviral vector, MS3-WT1-siTCR composed of DNAs encoding WT1235-243/HLA-A*24:02 complex specific TCR-α/β chains and siRNAs against endogenous TCR genes. Expanded gene-modified lymphocytes (WT1-siTCR/T cells) in additional culture for 13-14 more days were harvested and frozen until use. Eligibility included HLA-A*24:02 positive pts with refractory AML or high-risk MDS, &gt; 20 y.o, ineligible for allo-HSCT and performance status of 0 to 2. WT1-siTCR/T cells were intravenously infused twice on days 0 and 28. Heteroclitic WT1235-243 ninemer peptide (300mg) emulsified with MontanideTM was given subcutaneously on day 2 and 16 after the second infusion. Besides safety assays, kinetics of WT1-siTCR/T cells in PB, immunological responses and residual leukemia burden determined by qRT-PCR for WT1 mRNA were serially measured until day 58 since the first infusion.


    Among 12 pts enrolled, 8 pts (5 AML, 3 MDS) with a median age of 68.5 y. received study treatment. Three pts received 2x108 cells/ infusion (cohort 1), 3 received 1x109 cells/ infusion (cohort 2), and 2 received extra-cohort doses. Median follow-up time after the first infusion was 257 days (as June 13, 2016). At the first infusion, all pts contracted progressive disease. Circulatory WT1-siTCR/T cells retaining the target reactivity appeared immediately after each infusion, peaked between 1 to 3 days, and declined thereafter. WT1 peptide vaccination did not seem to affect the transition of infused cells. Values of WT1 mRNA in PB were transiently suppressed in all pts and declined in 4 pts thereafter. Clinical outcomes included one with stable disease and 2 pts with partial remission (PR). In one with PR, the epitope-spreading phenomenon was suggested. In all pts, no serious adverse events associated with infused WT1-siTCR/T cells were observed.


    Adoptive transfer of autologous WT1-siTCR/T cells was feasible and safe. Although the persistence of infused WT1-siTCR/T cells was limited, infused WT1-siTCR/T cells at least seemed to be involved in the antileukemia reactivity.


    <sec>
    <title>Disclosures</title>
    Tawara: Astellas: Honoraria. Akatsuka:Takara Bio Inc.: Consultancy. Nukaya:Takara Bio Inc.: Employment. Takesako:Takara Bio Inc.: Employment.


    </sec>

  23. 赤塚美樹.遺伝子改変T細胞療法の開発の歴史と将来. Invited International conference

    赤塚 美樹

    第78回日本血液学会総会.教育講演 49 

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    Event date: 2016.10

    Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  24. 遺伝子改変T細胞療法の開発の歴史と将来. International conference

    赤塚 美樹

    第78回日本血液学会総会 

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    Event date: 2016.10

    Language:Japanese  

    Country:Japan  

  25. t(4;12)を伴うAML症例におけるETV6転座によるPDGFRAおよびGSX2の転写活性化(Transcriptional activation of PDGFRA and GSX2 by ETV6 translocation in a case of AML with t(4;12))

    Abe Akihiro, Mizuta Shuichi, Yamamoto Yukiya, Okamoto Akinao, Iba Sachiko, Tokuda Masutaka, Inaguma Yoko, Yanada Masamitsu, Morishima Satoko, Kanie Tadaharu, Tomita Akihiro, Akatsuka Yoshiki, Okamoto Masataka, Kameyama Toshiki, Maeda Akira, Emi Nobuhiko

    臨床血液  2016.9  (一社)日本血液学会-東京事務局

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    Event date: 2016.9

    Language:English  

  26. DLBCL患者における単核球及び血清中と腫瘍中EBVウイルス量の関係

    岡本 晃直, 柳田 正光, 岡本 昌隆, 稲熊 容子, 徳田 倍将, 森島 聡子, 蟹江 匡治, 山本 幸也, 水田 秀一, 冨田 章裕, 赤塚 美樹, 吉川 哲史, 中村 栄男, 溝口 良順, 恵美 宣彦

    日本リンパ網内系学会会誌  2016.8  (一社)日本リンパ網内系学会

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    Event date: 2016.8

    Language:Japanese   Presentation type:Oral presentation (general)  

  27. Basics and development of CAR-T cell therapy and its clinical applications. Invited International conference

    赤塚 美樹

    第14回日本臨床腫瘍学会総会. 教育講演2 

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    Event date: 2016.7

    Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  28. 血液浄化・ステロイドパルスが奏効したEBV関連血球貪性リンパ組織球症の1例

    野村 宣徳, 岡本 晃直, 稲熊 容子, 徳田 倍将, 森島 聡子, 蟹江 匡治, 柳田 正光, 山本 幸也, 水田 秀一, 冨田 章裕, 赤塚 美樹, 岡本 昌隆, 恵美 宣彦

    臨床血液  2016.6  (一社)日本血液学会-東京事務局

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    Event date: 2016.6

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

  29. 当院における異型適合赤血球輸血の状況

    荒川 章子, 杉浦 縁, 松浦 秀哲, 松野 貴洋, 及川 彰太, 永田 梨奈, 磯貝 聡衣, 加藤 友理, 村松 知佳, 柴田 亜委, 倉橋 美千代, 岡本 晃直, 水田 秀一, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2016.6  (一社)日本輸血・細胞治療学会

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    Event date: 2016.6

    Language:Japanese  

  30. 輸血依存MDS及びAAにおける、デフェラシロクス時代の鉄過剰症及び生存/死因の検討

    岡本 晃直, 加藤 友理, 村松 知佳, 松浦 秀哲, 荒川 章子, 杉浦 縁, 徳田 倍将, 森島 聡子, 水田 秀一, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2016.4  (一社)日本輸血・細胞治療学会

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    Event date: 2016.4

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

  31. 当院における新生児・小児に対する赤血球輸血の後方視的検討

    加藤 友理, 松浦 秀哲, 永田 梨奈, 磯貝 聡衣, 村松 知佳, 荒川 章子, 倉橋 美千代, 杉浦 縁, 岡本 晃直, 水田 秀一, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2016.4  (一社)日本輸血・細胞治療学会

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    Event date: 2016.4

    Language:Japanese  

  32. 悪性リンパ腫における末梢血EBV-DNA量測定の意義

    岡本 晃直, 柳田 正光, 三浦 浩樹, 稲熊 容子, 德田 倍将, 蟹江 匡治, 山本 幸也, 冨田 章裕, 赤塚 美樹, 岡本 昌隆, 吉川 哲史, 恵美 宣彦

    藤田学園医学会誌  2016  藤田学園医学会

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    Event date: 2016

    Language:Japanese  

  33. Adoptive Transfer of WT1-Specific TCR Gene-Transduced Lymphocytes in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia International conference

    Isao Tawara, Masahiro Masuya, Shinichi Kageyama, Tetsuya Nishida, Seitaro Terakura, Makoto Murata, Hiroshi Fujiwara, Yoshiki Akatsuka, Hiroaki Ikeda, Yoshihiro Miyahara, Daisuke Tomura, Ikuei Nukaya, Kazutoh Takesako, Nobuhiko Emi, Masaki Yasukawa, Naoyuki Katayama, Hiroshi Shiku

    Blood  2015.12.3  American Society of Hematology

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    Event date: 2015.12

    Language:English   Presentation type:Oral presentation (general)  

    <title>Abstract</title>
    Wilms' Tumor 1 (WT1) is expressed in a majority of MDS and AML cells and mRNA of WT1 in peripheral blood and bone marrow is monitored as a marker of minimal residual disease of AML and MDS. Several WT1 protein-derived epitopes that are recognized by cytotoxic T lymphocytes (CTLs) along with HLA molecules are determined. In vitro study and WT1 peptide vaccine trials have demonstrated that WT1-specfic CD8+ T cells with cytotoxic activity can be induced. Adoptive T cell therapy using ex vivo expanded WT1-specific CTLs or WT1-specific T-cell receptor (TCR)-gene transduced cells are potentially effective to refractory MDS and AML.


    Antigen-specific TCR-gene transfer may cause serious autoimmune disease by mispairing of introduced and endogenous TCR chains that recognize auto-antigens. We established a retroviral vector system encoding siRNAs for endogenous TCR genes to eliminate TCR-mispairing. Using the siRNA-encoding viral vector, we have conducted a first-in-man trial of WT1-specfic TCR-gene transduced T cell transfer. In the trial, we evaluate the safety of the TCR T cell transfer in patients with MDS and AML, and assess in vivo kinetics of the transferred cells. The study was designed as cell-dose escalation with three cohorts of 2x108, 1x109, and 5x109cells per infusion.


    Peripheral blood mononuclear cells were collected from each patient. Then, the cells were cultured with IL-2, anti-CD3 antibody, and RetroNectin®. Proliferating lymphocytes were infected with a retroviral vector, MS3-WT1-siTCR, which was constructed from DNA encoding WT1235-243/HLA*A24:02 specific TCR-α and -β chains and siRNAs for endogenous TCR genes. After 13-14 days in culture, the lymphocytes were harvested and frozen until infusion.


    Patients were enrolled to the clinical trial if they were refractory AML or MDS ineligible for allogeneic stem cell transplant, positive for HLA-A*24:02, had performance status of 0 to 2, and had normal organ function. WT1-TCR T cells were infused intravenously twice on days 0 and 28. Modified WT1235-243peptide (300μg) emulsified with Montanide, was given subcutaneously on day 2 and 16 after the second infusion.


    To date, 5 patients (4 MDS and 1 AML cases) with a median age of 69 years, received WT1-TCR T cells. Three received 2x108 cells (cohort 1) and 2 received 1x109 cells (cohort 2) per infusion, respectively. We did not see any severe adverse events related to the cell infusion or peptide vaccination. No renal or mesothelial damages were observed. We then assessed transduced TCR-gene copy numbers in peripheral blood samples collected at multiple pre-determined time points until day 58.TCR-gene marked cells were detected in all patients after the cell infusion. They appeared immediately after the infusion, reaching peak levels between 1 and 3 days. Then, the levels gradually declined. After the second infusion, which was followed by peptide vaccination, the cells appeared in the similar way to the first cycle. The peptide vaccine did not seem to affect the peripheral cell kinetics. Dose-dependent kinetics were shown between the cohort 1(2 x108 cells) and the cohort 2 (1x109cells). In two patients, transient decline of peripheral abnormal cells that were MDS-related erythroblasts, and decrease of bone marrow blasts were observed, respectively.


    Although the clinical trial is still ongoing, transfer of WT1-TCR-gene transduced lymphocyte to MDS and AML patients is safe and tolerable. TCR- T cells appeared in peripheral blood with cell-dose dependent manner.


    <sec>
    <title>Disclosures</title>
    Fujiwara: Celgene: Honoraria, Other: Travel, Acomodations, Expenses. Akatsuka:Takara Bio. Inc.: Other: Advisor to the CAR project. Tomura:TAKARO BIO INC.: Employment. Nukaya:TAKARA BIO INC.: Employment. Takesako:TAKARA BIO INC.: Employment.


    </sec>

  34. B型肝炎キャリアの初回妊娠中に発症した重症再生不良性貧血(SAA)の1例

    栗本 恭好, 蟹江 匡治, 岡本 晃直, 稲熊 容子, 徳田 倍将, 柳田 正光, 森島 聡子, 山本 幸也, 水田 秀一, 赤塚 美樹, 岡本 昌隆, 恵美 宣彦

    臨床血液  2015.11  (一社)日本血液学会-東京事務局

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    Event date: 2015.11

    Language:Japanese  

  35. 導入化学療法を受けない急性骨髄性白血病患者の転帰(The fate of patients with acute myeloid leukemia not undergoing induction chemotherapy)

    Yanada Masamitsu, Okamoto Akinao, Inaguma Yoko, Tokuda Masutaka, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Mizuta Shuichi, Akatsuka Yoshiki, Okamoto Masataka, Emi Nobuhiko

    臨床血液  2015.9  (一社)日本血液学会-東京事務局

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    Event date: 2015.9

    Language:English   Presentation type:Oral presentation (general)  

  36. t(8;14;18)(q24;q32;q21)を有するDLBCLとBLの中間型リンパ腫(Intermediate lymphoma between DLBCL and BL with t(8;14;18) (q24;q32;q21))

    Inaguma Yoko, Okamoto Akinao, Ito Kaori, Tokuda Masutaka, Yanada Masamitsu, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Mizuta Shuichi, Akatsuka Yoshiki, Okamoto Masataka, Emi Nobuhiko

    臨床血液  2015.9  (一社)日本血液学会-東京事務局

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    Event date: 2015.9

    Language:Japanese  

  37. t(8;12;21)のRUNX1-RUNX1T1白血病において発見されたTM7SF4-VPS13BおよびVPS13B-RUNX1融合遺伝子(TM7SF4-VPS13B and VPS13B-RUNX1 fusion genes found in RUNX1-RUNX1T1 leukemia with t(8;12;21))

    Abe Akihiro, Yamamoto Yukiya, Okamoto Akinao, Tokuda Masutaka, Inaguma Yoko, Yamamoto Kiyoko, Yanada Masamitsu, Morishima Satoko, Kanie Tadaharu, Mizuta Syuichi, Akatsuka Yoshiki, Okamoto Masataka, Kameyama Toshiki, Mayeda Akila, Emi Nobuhiko

    臨床血液  2015.9  (一社)日本血液学会-東京事務局

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    Event date: 2015.9

    Language:English  

  38. DLBCL患者の処置前血清におけるEBV DNA検出の予後的意義(Prognostic significance of EBV DNA detection in pretreatment serum from patients with DLBCL)

    Okamoto Akinao, Yanada Masamitsu, Okamoto Masataka, Miura Hiroki, Inaguma Yoko, Tokuda Masutaka, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Mizuta Shuichi, Akatsuka Yoshiki, Yoshikawa Tetsushi, Mizoguchi Yoshikazu, Nakamura Shigeo, Emi Nobuhiko

    臨床血液  2015.9  (一社)日本血液学会-東京事務局

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    Event date: 2015.9

    Language:Japanese   Presentation type:Oral presentation (general)  

  39. Bendamustineとrituximab併用による再治療の免疫系に対する有効性、毒性および影響(Efficacy, toxicity and effect on the immune system of retreatment with bendamustine plus rituximab)

    Ito Kaori, Okamoto Masataka, Ando Maiko, Ando Yosuke, Kakumae Yukiko, Okamoto Akinao, Inaguma Yoko, Tokuda Masutaka, Yanada Masamitsu, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Mizuta Syuichi, Hayashi Takahiro, Akatsuka Yoshiki, Yamada Shigeki, Emi Nobuhiko

    臨床血液  2015.9  (一社)日本血液学会-東京事務局

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    Event date: 2015.9

    Language:Japanese  

  40. 最重症再生不良性貧血の一例

    水谷 有希, 佐藤 聖子, 大澤 道子, 西井 智香子, 松浦 秀哲, 杉浦 縁, 稲熊 容子, 赤塚 美樹, 恵美 宣彦

    日本検査血液学会雑誌  2015.6  (一社)日本検査血液学会

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    Event date: 2015.6

    Language:Japanese  

  41. 藤田保健衛生大学病院輸血タスクフォースの取り組み

    松浦 秀哲, 水田 秀一, 杉浦 縁, 橋本 さや香, 荒川 章子, 村山 元秀, 高木 里枝, 関谷 佳代, 石神 泰子, 岡松 幸代, 大川 千春, 酒井 敏江, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2015.4  (一社)日本輸血・細胞治療学会

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    Event date: 2015.4

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

  42. 血液悪性腫瘍を発症した患者の微量元素、ビタミンの血中濃度の検討

    徳田 倍将, 稲熊 容子, 蟹江 匡治, 山本 幸也, 柳田 正光, 水田 秀一, 赤塚 美樹, 岡本 昌隆, 恵美 宣彦

    日本内科学会雑誌  2015.2  (一社)日本内科学会

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    Event date: 2015.2

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

  43. 末梢血幹細胞採取量予測に関する検討

    杉浦 縁, 松浦 秀哲, 水田 秀一, 永田 梨奈, 沼尻 茜, 加藤 友理, 村松 知佳, 村山 元秀, 荒川 章子, 倉橋 美千代, 岡本 晃直, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2015.2  (一社)日本輸血・細胞治療学会

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    Event date: 2015.2

    Language:Japanese   Presentation type:Oral presentation (general)  

  44. 当院における輸血副作用発生状況の検討

    加藤 友理, 松浦 秀哲, 永田 梨奈, 沼尻 茜, 村松 知佳, 村山 元秀, 荒川 章子, 倉橋 美千代, 杉浦 縁, 岡本 晃直, 水田 秀一, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2015.2  (一社)日本輸血・細胞治療学会

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    Event date: 2015.2

    Language:Japanese   Presentation type:Oral presentation (general)  

  45. 私のこの一枚 症例報告 HLH軽快後にB細胞リンパ腫の診断に至った1例

    稲熊 容子, 赤塚 美樹, 岡本 昌隆, 恵美 宣彦

    血液フロンティア  2015.1  (株)医薬ジャーナル社

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    Event date: 2015.1

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

  46. EBV‐positive diffuse large B‐cell lymphoma of the elderlyの臨床病理学的検討

    OKAMOTO AKINAO, OKAMOTO MASATAKA, YANADA MASAMITSU, INAGUMA YOKO, MORISHIMA SATOKO, KANIE TADAHARU, YAMAMOTO YUKIYA, MIZUTA SHUICHI, AKATSUKA YOSHIKI, EMI NOBUHIKO

    日本臨床腫瘍学会学術集会(CD-ROM)  2015 

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    Event date: 2015

    Language:Japanese  

  47. びまん性大細胞型B細胞リンパ腫におけるEBV量とEBER陽性の予後的意義(The prognostic significance of EBV viral load and EBER-positivity in diffuse large B-cell lymphoma)

    Okamoto Akinao, Yanada Masamitsu, Okamoto Masataka, Inaguma Yoko, Tokuda Masutaka, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Abe Akihiro, Mizuta Shuichi, Akatsuka Yoshiki, Yoshikawa Tetsushi, Emi Nobuhiko

    臨床血液  2014.9  (一社)日本血液学会-東京事務局

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    Event date: 2014.9

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

  48. DEK-NUP214を伴うAML患者における付加的なNUP214-RAC1融合遺伝子(Additional NUP214-RAC1 fusion gene in an AML patient with DEK-NUP214)

    Abe Akihiro, Yamamoto Yukiya, Okamoto Akinao, Tokuda Masutaka, Inaguma Yoko, Yanada Masamitsu, Morishima Satoko, Kanie Tadaharu, Tsuzuki Motohiro, Akatsuka Yoshiki, Mizuta Shuichi, Okamoto Masataka, Kameyama Toshiki, Mayeda Akira, Emi Nobuhiko

    臨床血液  2014.9  (一社)日本血液学会-東京事務局

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    Event date: 2014.9

    Language:English  

  49. 慢性骨髄性白血病患者の治療中に生じた最重症再生不良性貧血

    山添 泰佳, 岡本 晃直, 稲熊 容子, 徳田 倍将, 森島 聡子, 柳田 正光, 蟹江 匡治, 山本 幸也, 赤塚 美樹, 水田 秀一, 岡本 昌隆, 恵美 宣彦

    臨床血液  2014.7  (一社)日本血液学会-東京事務局

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    Event date: 2014.7

    Language:Japanese  

  50. 異なった親和性をもつHLA-A2拘束性マイナー抗原HA-1Hを特異的CAR-T細胞の機能解析

    赤塚 美樹, 赤堀 泰, 稲熊 容子, 西村 泰治, 岡村 文子, 葛島 清隆, 恵美 宣彦

    日本がん免疫学会総会プログラム・抄録集  2014.6  日本がん免疫学会

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    Event date: 2014.6

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

  51. カリウム吸着フィルターを使用した小児輸血の基礎的検討

    杉浦 縁, 松浦 秀哲, 加藤 友理, 村松 知佳, 沼尻 茜, 村山 元秀, 荒川 章子, 倉橋 美千代, 高須賀 広久, 赤塚 美樹, 水田 秀一, 恵美 宣彦

    日本輸血細胞治療学会誌  2014.6  (一社)日本輸血・細胞治療学会

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    Event date: 2014.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  52. Angiommunoblastic T-cell lymphoma(AITL)の自家造血幹細胞移植(auto HSCT)後にB細胞リンパ増殖性疾患を発症した一例

    岡本 晃直, 岡本 昌隆, 稲熊 容子, 徳田 倍将, 森島 聡子, 柳田 正光, 蟹江 匡治, 山本 幸也, 水田 秀一, 赤塚 美樹, 恵美 宣彦

    日本リンパ網内系学会会誌  2014.6  (一社)日本リンパ網内系学会

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    Event date: 2014.6

    Language:Japanese  

  53. 急速大量輸血を想定したカリウム吸着フィルターの検討

    村松 知佳, 松浦 秀哲, 磯貝 聡衣, 杉浦 縁, 沼尻 茜, 加藤 友理, 村山 元秀, 荒川 章子, 倉橋 美千代, 高須賀 広久, 赤塚 美樹, 水田 秀一, 恵美 宣彦

    日本輸血細胞治療学会誌  2014.4  (一社)日本輸血・細胞治療学会

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    Event date: 2014.4

    Language:Japanese  

  54. 当院における緊急O型赤血球輸血依頼状況

    磯貝 聡衣, 松浦 秀哲, 高須賀 広久, 倉橋 美千代, 杉浦 縁, 荒川 章子, 村山 元秀, 内田 由香, 村松 知佳, 長谷川 勝俊, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2013.10  (一社)日本輸血・細胞治療学会

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    Event date: 2013.10

    Language:Japanese  

  55. TRAILを発現する多能性幹細胞由来ミエロイド細胞を用いた細胞医薬の開発(Pluripotent stem cell-derived myeloid cells engineered to express TRAIL as a possible cell medicine for cancer)

    牧 寛之, 植村 靖史, 張 エイ, 竹田 和由, 劉 天懿, 鈴木 元晴, 都築 忍, 岡村 文子, 赤塚 美樹, 西村 泰治, 千住 覚, 葛島 清隆

    日本癌学会総会記事  2013.10  日本癌学会

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    Event date: 2013.10

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

  56. 第1選択R-CHOP療法が濾胞性リンパ腫患者の免疫に及ぼす影響(Effects of 1st line R-CHOP on the immunity in patients with follicular lymphoma)

    Ito Kaori, Okamoto Masataka, Terazawa Tomohiko, Kakumae Yukiko, Okamoto Akinao, Inaguma Yoko, Tokuda Masutaka, Yanada Masamitsu, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Akatsuka Yoshiki, Mizuta Shuichi, Yamada Shigeki, Emi Nobuhiko

    臨床血液  2013.9  (一社)日本血液学会-東京事務局

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    Event date: 2013.9

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

  57. 当院診療部門における輸血管理状況

    荒川 章子, 長谷川 勝俊, 高須賀 広久, 倉橋 美千代, 杉浦 縁, 村山 元秀, 内田 由香, 松浦 秀哲, 村松 知佳, 磯貝 聡江, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2013.4  (一社)日本輸血・細胞治療学会

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    Event date: 2013.4

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

  58. リツキシマブの開発前後の無作為に選んだDLBCL患者の治療成績の違い(Differences in outcome for unselected patients with DLBCL before and after the advent of rituximab)

    Okamoto Akinao, Yanada Masamitsu, Inaguma Yoko, Tokuda Masutaka, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Tuzuki Motohiro, Akatsuka Yoshiki, Shuichi Mizuta, Okamoto Masataka, Emi Nobuhiko

    臨床血液  2012.9  (一社)日本血液学会-東京事務局

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    Event date: 2012.9

    Language:English  

  59. NUP98-HOXA9のAML再発患者に見られたt(11;12)(q13;p13)の追加よるETV6-LPXN融合遺伝子(ETV6-LPXN fusion from additional t(11;12) (q13;p13) in a patient relapsing with AML with NUP98-HOXA9)

    Akihiro Abe, Kanie Tadaharu, Yamamoto Yukiya, Okamoto Akinao, Tokuda Masutaka, Inaguma Yoko, Yanada Masamitsu, Morishima Satoko, Akatsuka Yoshiki, Mizuta Syuichi, Okamoto Masataka, Emi Nobuhiko

    臨床血液  2012.9  (一社)日本血液学会-東京事務局

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    Event date: 2012.9

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

  60. 当院で検出された抗K抗体の1症例

    杉浦 縁, 長谷川 勝俊, 高須賀 広久, 倉橋 美千代, 荒川 章子, 村山 元秀, 内田 由香, 松浦 秀哲, 村上 優佳, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2012.4  (一社)日本輸血・細胞治療学会

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    Event date: 2012.4

    Language:Japanese  

  61. 劇症型心筋炎に免疫グロブリン大量療法が奏効した1症例

    松浦 秀哲, 長谷川 勝俊, 高須賀 広久, 倉橋 美千代, 杉浦 縁, 荒川 章子, 村山 元秀, 内田 由香, 村上 優佳, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2012.4  (一社)日本輸血・細胞治療学会

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    Event date: 2012.4

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

  62. 当科でのDIC症例に関する検討(Single center analysis of DIC with hematological malignancy)

    稲熊 容子, 岡本 晃直, 徳田 倍将, 柳田 正光, 森島 聡子, 蟹江 匡治, 山本 幸也, 都築 基弘, 赤塚 美樹, 水田 秀一, 岡本 昌隆, 恵美 宣彦

    Thrombosis Medicine  2012.3  (株)先端医学社

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    Event date: 2012.3

    Language:Japanese  

  63. 当院におけるPBSCの現状

    杉浦縁, 長谷川勝俊, 倉橋美千代, 村山元秀, 七ツ村めぐみ, 水田秀一, 赤塚美樹, 恵美宣彦

    日本輸血細胞治療学会誌  2012.2.25 

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    Event date: 2012.2

    Language:Japanese   Presentation type:Oral presentation (general)  

  64. Intracellular interferon-γ staining analysis of donor-specific t-cell responses in liver transplant recipients

    Y. Okanami, K. Tsujimura, S. Mizuno, M. Tabata, S. Isaji, Y. Akatsuka, K. Kuzushima, T. Takahashi, S. Uemoto

    Transplantation Proceedings  2012 

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    Event date: 2012

    Language:English  

  65. 血液悪性腫瘍を伴うDICに関する単施設での解析(Single center analysis of DIC with hematologicalmalignancy)

    Inaguma Yoko, Okamoto Akinao, Tokuda Masutaka, Yanada Masamitsu, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Tsuzuki Motohiro, Akatsuka Yoshiki, Mizuta Shuichi, Okamoto Masataka, Emi Nobuhiko

    臨床血液  2011.9  (一社)日本血液学会-東京事務局

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    Event date: 2011.9

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

  66. FLT3シグナル伝達を直接調節するヒト単クローン抗体の分離(Isolation of human monoclonal antibodies directly modulating FLT3 signaling)

    Yamamoto Yukiya, Tsuzuki Sachiko, Akahori Yasushi, Ukai Yoshinori, Sumitomo Mariko, Tokuda Masutaka, Kanie Tadaharu, Abe Akihiro, Akatsuka Yoshiki, Kurosawa Yoshikazu, Emi Nobuhiko

    臨床血液  2011.9  (一社)日本血液学会-東京事務局

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    Event date: 2011.9

    Language:Japanese  

  67. Deferasiroxを投与したMDS患者2例における造血に及ぼす好ましい効果(Positive effects on hematopoiesis in two patients with MDS receiving deferasirox)

    Tsuzuki Motohiro, Inaguma Youko, Okamoto Akiao, Tokuda Masutaka, Yanada Masamitsu, Morishima Satoko, Kanie Tadaharu, Yamamoto Yukiya, Akatsuka Yoshiki, Mizuta Shuichi, Okamoto Masataka, Emi Nobuhiko

    臨床血液  2011.9  (一社)日本血液学会-東京事務局

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    Event date: 2011.9

    Language:English  

  68. マイナー組織適合抗原の重要性 Invited International conference

    赤塚 美樹

    第33回日本造血細胞移植学会 

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    Event date: 2011.3

    Country:Japan  

  69. 当院における輸血関連インシデント事例の検討

    松浦 秀哲, 長谷川 勝俊, 倉橋 美千代, 杉浦 縁, 荒川 章子, 村山 元秀, 内田 由香, 七ツ村 めぐみ, 村上 優佳, 高須賀 広久, 富井 榮江, 赤塚 美樹, 恵美 宣彦

    日本輸血細胞治療学会誌  2011.3  (一社)日本輸血・細胞治療学会

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    Event date: 2011.3

    Language:Japanese   Presentation type:Oral presentation (general)  

  70. 臍帯血移植後にオセルタミビル耐性新型インフルエンザ(H1N1)感染により死亡した成人APLの1例

    都築基弘, 半田幸助, 稲熊容子, 徳田倍将, 長谷川明生, 森島聡子, 蟹江匡治, 山本幸也, 赤塚美樹, 水田秀一, 岡本昌隆, 恵美宣彦

    日本造血細胞移植学会総会プログラム・抄録集  2011 

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    Event date: 2011

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

  71. 末梢血CD34陽性細胞とCD34陽性細胞収量の相関

    杉浦縁, 水田秀一, 長谷川勝俊, 倉橋美千代, 荒川章子, 村山元秀, 七ツ村めぐみ, 内田由香, 村上優佳, 高須賀広久, 富井栄江, 赤塚美樹, 恵美宣彦, 恵美宣彦

    日本輸血細胞治療学会誌  2010.4.28 

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    Event date: 2010.4

    Language:Japanese   Presentation type:Oral presentation (general)  

  72. 低悪性度B細胞リンパ腫に対するFludarabinおよびRituximab‐Fludarabin療法の有害事象;免疫機能に与える影響を中心に

    熊澤里美, 岡本昌隆, 伊藤佳織, 稲熊容子, 太田秀基, 山本幸也, 都築基弘, 水田秀一, 赤塚美樹, 丸山文夫, 矢野裕章, 恵美宣彦

    日本臨床腫瘍学会学術集会プログラム・抄録集  2010 

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    Event date: 2010

    Language:Japanese  

  73. 造血幹細胞移植と組織適合性抗原 同種造血幹細胞移植とマイナー組織適合性抗原 Invited International conference

    赤塚 美樹

    第18回日本組織適合性学会 

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    Event date: 2009.9

    Country:Japan  

  74. 網羅的ゲノム解析によるB細胞性リンパ腫における標的遺伝子A20の同定

    加藤 元博, 真田 昌, 加藤 格, 佐藤 康晴, 滝田 順子, 竹内 賢吾, 丹羽 明, 陳 玉彦, 中崎 久美, 野本 順子, 朝倉 義崇, 赤塚 美樹, 林 泰秀, 五十嵐 隆, 黒川 峰夫, 千葉 滋, 森 茂郎, 石川 雄一, 岡本 康司, 飛内 賢正, 中釜 斉, 中畑 龍俊, 吉野 正, 小林 幸夫, 小川 誠司

    日本リンパ網内系学会会誌  2009.6  (一社)日本リンパ網内系学会

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    Event date: 2009.6

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

  75. Genome-Wide Association Studies of Genetic Incompatibility That Is Relevant to the Development of GvHD in Unrelated Bone Marrow Transplantation International conference

    Seishi Ogawa, Aiko Matsubara, Koichi Kashiwase, Makoto Onizuka, Masashi Sanada, Motohiro Kato, Yasuhito Nannya, Yoshiki Akatsuka, Takakazu Kawase, Masahiro Satake, Junko Takita, Yasuo Morishima, Shigeru Chiba, Hiroo Saji, Hidetoshi Inoko, Yoshihisa Kodera, Takehiko Sasazuki

    Blood  2008.11.16  American Society of Hematology

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    Event date: 2008.11

    Language:English   Presentation type:Oral presentation (general)  

    <title>Abstract</title>
    Allogeneic stem cell transplantation (allo-SCT) is one of the most effective therapeutic options for blood cell cancers. While its major anti-leukemic benefits are obtained from allo-immune reactions against leukemic cells, or GVL, the same kind of allo-reactions could be also directed to normal host tissues, giving rise to a severe complication, know as graft versus host disease (GvHD). In HLA-matched transplantation, the development of both reactions absolutely depends on the presence of one or more mismatched minor histocompatibility antigens (mHAgs) and could be further modified by other genetic as well as environmental factors, including for example, cytokine polymorphisms and GvHD prophylaxis. Thus, in view of better preventing GvHD and specifically targeting allo-immunity to the tumor component, it is critical to understand what mHAgs are mismatched and responsible for the development of GVHD or GVL and what genetic factors can influence the overall reactions. To address these questions, we conducted whole genome association studies by genotyping more than 500,000 SNPs in donors and recipients of 1598 unrelated transplants from Japan Marrow Donation Program (JMDP). All transplants were matched for HLA-A, B, C, DRB1 and DQB1, while 1033 (63%) transplants were mismatched for HLA-DPB1. 656 (41.7%) and 245 (14.9%) of transplants had developed grade II–IV and III–IV of acute GvHD (aGvHD), respectively. Overall call rates exceeded 98% both in donors and in recipients. Unobserved HapMap PhaseII SNPs were rigorously imputed using genotyped SNPs. After excluding those SNPs showing &lt;95% call rate, deviation from Hardy-Weinberg equilibrium, or &lt;5% minor allele frequency, 1,276,699 SNPs were tested for association with development of acute and chronic GvHD, relapse, and overall survival, by calculating LogRank statistics for each SNP according to single genotypes in donors and recipients or based on mismatch in genotypes between donor and recipient. Statistical thresholds for genome-wide-P value of 0.05 were determined empirically by doing 1,000 permutations for each analysis. In the analysis of mismatched genotypes, SNPs around the HLA-DPB1 locus uniquely showed a strong association with the development of &gt;grade II aGvHD with the maximum P-value of 1.81 × 10−9 at rs6937034, and thus, successfully captured the association of DPB1 allele mismatch as directly defined by HLA typing (HR = 1.91, P= 2.88 × 10−13). To facilitate the identification of target mHAgs for aGvHD, we performed subgroup analysis, where association tests were confined to those transplants sharing particular HLA types based on the fact that recognition of mHAgs is restricted to particular HLA contexts (HLA restriction). Six loci was identified as candidate mHAg loci whose mismatch may confer increased risk for development of aGvHD. These included rs17473423 on chr12 associated with an A*2402/B*5201/Cw*1202/DRB1*1501/DQB1*0601 allele set shared in ~40% of unrelated transplants in Japanese (grade III–IV aGvHD with maximum P=3.99 × 10−13), rs9657655 on chr9 associated with another common allele in Japanese, A*3303/B*4403/Cw*1403 (grade III–IV aGvHD with maximum P=8.56 × 10−10), and other four loci associated with DQB1*0501, Cw*0102, B*5201, and Cw*1202. Two SNPs in patients were also found to be associated with aGvHD, rs5998746 on chr22 (P=3.41 × 10−8) and rs11873016 on chr18 (P=1.26 × 10−8), although no donor SNPs showed significant associations). Similarly, we identified four candidate SNPs associated with the development of severe cGvHD or relapse. Current study provided a unique opportunity in that combination of two different genotypes, not merely genotypes of single individuals, that is associated with particular disease phenotypes, is explored by whole genome association scans. Although further replication studies and biological confirmation are required, our results suggest that whole genome association studies of allo-SCT could provide a novel clue to understanding the genetic basis of allo-SCT.

  76. 骨髄移植症例に誘導されるGVL効果の解析. Invited International conference

    赤塚 美樹

    第67回日本癌学会総会 シンポジウム 

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    Event date: 2008.9

    Country:Japan  

  77. Minor Antigen 反応性CTLの移植医療への関与 Invited International conference

    赤塚 美樹

    第31回日本造血細胞移植学会総会、シンポジウム 

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    Event date: 2008.2

    Country:Japan  

  78. Escape of Minor Histocompatibility Antigen-Restricted Anti-Leukemia Immunity Associated with Loss of Specific HLA-I Locus Expression in a Leukemia Patient after an Intensive Immunotherapy. International coauthorship International conference

    Lung-Ji Chang, Chun-Rong Tong, Jih-Luh Tang, Yoshiki Akatsuka, Shuhong Han, Yin Liang, Chi-Cheng Li, Lujia Dong, Tong Wu, Dao-Pei Lu

    Blood  2007.11.16  American Society of Hematology

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    Event date: 2007.11

    Language:English  

    <title>Abstract</title>
    Differential graft versus host response after bone marrow transplantation (BMT) is key to leukemia patient survival. The development of specific graft versus leukemia response targeting tissue-specific minor histocompatibility antigens (mHAgs) is a novel therapeutic approach to treating hematopoietic malignancies. A pilot intensive immune cell therapy was applied to an acute myeloid leukemia (AML) patient who relapsed around day 43 after receiving unrelated allogeneic BMT with three allele disparities for HLA-A, C and DQB1. The patient received more than thirty infusions of dendritic cell-co-cultured donor-derived immune cells including cytotoxic T lymphocytes (CTL) generated against AML lysate-pulsed dendritic cells (DC), AML-DC fusion, and DC pulsed with HLA-A*2402-restricted ACC1Y mHAg epitope. The latter was expressed by recipient but not by donor hematopoietic cells. ACC1Y-peptide-major histocompatibility complex (MHC) multimer staining detected CTL in the patients peripheral blood at different time points during treatment. Four months after the first mHAg-CTL infusion, CTL-resistant AML cells were detected in relapsed pleural effusion and peripheral blood. Further analysis of the relapsed AML cells revealed complete loss of surface class I HLA-A*2402 and class II HLA molecules. Although the AML-specific immune cells were effective in killing the original AML in CTL assays in vitro, the late relapsed AML became resistant to the early AML-primed CTL. This result suggests that rapidly evolving AML cells may escape the intensive anti-leukemia allo-immune pressure including the mHAg-specific CTL through selective loss of A*2402 expression - the ACC1Y-restricted HLA locus. As the patient suffered ongoing multi-focal extramedullary relapse in muscles, sub-mucosal tissue, intestine, spinal cord, and brain, rare cancer cells resistant to mHAg-specific CTL could evolve quickly. Our study indicates that immune escape through diminished HLA expression, which resulted in lack of cancer cell killing by AML-specific immune cells, including the mHAg-restricted CTL, had developed during the therapy. Therefore, leukemia patients with high load of AML or multi-focal extramedullary relapse may not endure prolonged benefit from a single arm immune cell therapy.

  79. GVHDを増強せずにGVL効果を高める治療法の可能性 Invited International conference

    赤塚 美樹

    第69回日本血液学会・第49回日本臨床血液学会 シンポジウム 

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    Event date: 2007.10

    Country:Japan  

  80. 造血器腫瘍に対する細胞免疫療法の今後 Invited International conference

    赤塚 美樹

    第69回日本血液学会・第49回日本臨床血液学会 

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    Event date: 2007.10

    Country:Japan  

  81. 臍帯血移植後に増加するCD16+CD56‐NK細胞がGvL効果に関与している

    盧緒章, 近藤恭夫, 高松博幸, 大畑欣也, 石山謙, 山崎宏人, 高見昭良, 奥村廣和, 赤塚美樹, 中尾眞二

    臨床血液  2007.9.30 

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    Event date: 2007.9

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

  82. BCL2A1にコードされる血液細胞特異的マイナー組織適合抗原のメラノーマにおける異所性発現(Aberrant Expression of BCL2A1-Encoded Minor Histocompatibility Antigens in Melanoma Cells)

    鳥飼 宏基, 赤塚 美樹, 谷田部 恭, 亀井 美智, 森島 泰雄, 小寺 良尚, 高橋 利忠, 葛島 清隆

    日本癌学会総会記事  2007.8  日本癌学会

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    Event date: 2007.8

    Language:English   Presentation type:Oral presentation (general)  

  83. マイナー組織適合抗原を標的とした免疫療法. Invited International conference

    赤塚 美樹

    第55回日本輸血・細胞治療学会総会 

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    Event date: 2007.5

    Country:Japan  

  84. Impact of Homozygous Deletion of UGT2B17 on Outcome of Allogeneic BMT. International coauthorship International conference

    Seitaro Terakura, Makoto Murata, Tetsuya Nishida, Nobuhiko Emi, Yoshiki Akatsuka, Stanley R. Riddell, Yasuo Morishima, Yoshihisa Kodera, Tomoki Naoe

    Blood  2004.11.16  American Society of Hematology

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    Event date: 2004.11

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

    <title>Abstract</title>
    We recently identified a human minor histocompatibility (H) antigen encoded by the UDP glycosyltransferase 2 family, polypeptide B17 (UGT2B17) gene. UGT2B17 is a metabolic enzyme that is highly expressed in liver and colon, and at low levels in hematopoietic cells. UGT2B17 conjugates exogenous and endogenous compounds including steroid hormones and facilitates their elimination. The immunogenicity of the UGT2B17 was due to differential expression of the protein in donor and recipient cells as a consequence of a homozygous deletion of the UGT2B17 gene in the recipient. Deletion of this gene in a subset of normal individuals suggested two mechanisms by which UGT2B17 could affect the outcome of allogeneic BMT. First, the expression of UGT2B17 in recipient but not donor cells could provide minor H antigens and increase GVHD. Second, the presence of UGT2B17 in the donor or recipient could affect the metabolism, function, or toxicity related to endogenous hormones or drugs administered with BMT. The purposes of this study were to determine the frequency of homozygous UGT2B17 deletion in healthy individuals and patients with hematological disease and whether a deficiency of UGT2B17 in donor and/or recipient affected the outcome of allogeneic BMT. A total of 435 recipients were selected from the patients who received unrelated BMT through the Japanese Marrow Donor Program between January 1993 and March 2000. Selection criteria were (1) matched at HLA-A, B, C and DRB1 genotypes, (2) unmanipulated marrow graft, (3) cyclosporine A or tacrolimus as GVHD prophylaxis, and (4) available DNA was stored. DNA from a total of 358 of the donors was also available. Homozygous deletion of the UGT2B17 gene determined by SSP-PCR was found in 320 (84.8%) of 377 donors and 358 (82.3%) of 435 patients (P=0.32, χ2 test). These frequencies of UGT2B17 deletion were substantially higher than the 11% observed in the Caucasian population in a previous study. A multivariate analysis (Cox proportional hazard model) showed no significant association between UGT2B17-mismatch in the GVHD direction and the incidence of acute GVHD (grade II-IV or III-IV), chronic GVHD, relapse, or survival. However, a deletion of UGT2B17 in the donor was a favorable factor for transplant-related mortality (TRM) (relative risk, 0.530; 95% CI, 0.334 to 0.841; P=0.007), survival (0.567; 0.387 to 0.831; P=0.036) and disease-free survival (DFS) (0.647; 0.443 to 0.945; P=0.024). We also analyzed these outcomes in the subset of patients with standard-risk malignant disease by the Kaplan-Meier method. TRM, survival, and DFS at eight years after transplantation were 23.7% for patients transplanted from a UGT2B17-deleted donor vs 52.9% for patients with a UGT2B17-positive donor (P=0.001); 68.3% vs 37.5% (P=0.0009); and 66.9% vs 37.5% (P=0.0009), respectively. These data suggest that the UGT2B17 enzyme in donor-derived blood cells may affect the metabolism of exogenously administered or endogenous molecules and adversely influence the outcome of unrelated BMT. Analysis in another patient population will be important to confirm our results.

  85. The status of the tumor microenvironment changes dynamics of the balance of CD8(+) T cells and Treg cells in renal cell carcinoma International conference

    Sugiyama Daisuke, Muramatsu Tomoaki, Kobayashi Yoichi, Sassa Naoto, Maruyama Shoichi, Goto Momokazu, Akatsuka Yoshiki, Nishikawa Hiroyoshi

    CANCER RESEARCH  2020.8 

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  86. 不適合 HLA-DP 抗原を標的とする同種移植後細胞免疫療法の検討

    勝山 直哉, 楫屋 良子, 白石 圭子, 西尾 信博, 一戸 辰夫, 赤塚 美樹

    第42回日本造血細胞移植学会総会  2020.3.6 

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  87. Tumor-infiltrating lymphocytes in renal cancer patients demonstrate a diverse PD-1 expression and characteristic Treg classification International conference

    Sugiyama Daisuke, Muramatsu Tomoaki, Kobayashi Yoichi, Sassa Naoto, Maruyama Shoichi, Goto Momokazu, Akatsuka Yoshiki, Nishikawa Hiroyoshi

    CANCER RESEARCH  2019.7 

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    Language:English  

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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. 11

  1. 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

    科学技術振興調整費 

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    Authorship:Principal investigator  Grant type:Competitive

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

  2. 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

  3. 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

  4. MS3-WT1-siTCR ベクターを用いたWT1 抗原特異的TCR遺伝子導入T リンパ球輸注による急性骨髄性白血病及び骨髄異形成症候群に対する遺伝子治療臨床研(分担)

    2015.4 - 2016.3

    研究開発施設共用等促進費補助金  

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    Authorship:Coinvestigator(s)  Grant type:Competitive

  5. がん特異的細胞性免疫の活性化を基盤とする新たな治療の開発(分担) International coauthorship

    Grant number:201313019B  2010.4 - 2014.3

    厚生労働科学研究費補助金  厚生労働科学研究費補助金

    葛島清隆、赤塚美樹、神田 輝、藤田 貢、岡村 文子

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\52914000

  6. 灌流法により採取された骨髄細胞を用いた骨髄内骨髄移植療法:基礎から臨床へ(分担)

    Grant number:201229009B  2010.4 - 2013.3

    厚生労働省研究事業  厚生労働科学研究費補助金

    池原進、赤塚美樹、一戸辰夫、小川啓恭、小島勢二、品川克至、森尾友宏、村田誠、森眞一郎、野村昌作

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\21407000

  7. 新しい造血幹細胞移植技術の開発に関する研究(分担)

    Grant number:200934031B  2008.4 - 2010.3

    厚生労働省研究事業  厚生労働科学研究費補助金

    池原進、赤塚美樹、一戸辰夫、小川啓恭、小島勢二、品川克至、森尾友宏

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\18800000

  8. 特異的細胞性免疫の活性化による新規がん治療の開発研究(分担)

    Grant number:200924026B  2007.4 - 2010.3

    厚生労働省研究事業  厚生労働科学研究費補助金

    葛島清隆、赤塚美樹、森島泰雄

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\46900000

  9. 「骨髄、末梢血等を利用した効率的な造血細胞移植の運用・登録と臨床試験体制の確立並びにドナー及びレシピエントの安全確保とQOL向上に関する研究」(分担)

    Grant number:200706013B  2005.4 - 2008.3

    厚生労働省研究事業  厚生労働科学研究費補助金

    小寺良尚、他19名

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\134758000

  10. テーラーメイド医療を目指したゲノム情報活用基盤技術-Whole Genome Association 解析によるGVHD の原因遺伝子の探索 (分担)

    2004.4 - 2009.3

    科学技術振興機構・戦略的創造研究推進事業 

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    Authorship:Coinvestigator(s) 

  11. がん特異的細胞傷害性T細胞活性化に基づく免疫治療の構築(分担)

    Grant number:200621021B  2004.4 - 2007.3

    厚生労働省研究事業  厚生労働科学研究費補助金

    葛島清隆、赤塚美樹、森島泰雄

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\54200000

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KAKENHI (Grants-in-Aid for Scientific Research) 12

  1. 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 )

  2. 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.

  3. 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 )

  4. マイナー抗原特異的免疫療法による免疫誘導能評価の標準化に関する研究

    Grant number:24591435  2012.4 - 2015.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\5200000 ( Direct Cost: \4000000 、 Indirect Cost:\1200000 )

  5. 造血幹細胞におけるHLAアレル欠失現象を利用した再生不良性貧血自己抗原の同定(分担)

    Grant number:23659486  2011.4 - 2013.3

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    中尾慎二、赤塚美樹

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

  6. マイナー抗原等に関与する責任SNPの新規同定法の開発とネットツールの公開

    Grant number:21591256  2009.4 - 2012.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    葛島 清隆

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    Authorship:Principal investigator 

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

  7. マイナー抗原を標的とした免疫療法の開発

    Grant number:17016089  2006.4 - 2009.3

    日本学術振興会  科学研究費助成事業  特定領域研究

    葛島清隆 、辻村邦夫

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\43200000 ( Direct Cost: \43200000 )

  8. マイナー抗原を標的とした免疫療法の開発(分担)

    Grant number:17016089  2005.4 - 2069.3

    日本学術振興会  科学研究費助成事業  特定領域研究

    高橋利忠、赤塚美樹、葛島清隆、辻村邦夫

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\43200000 ( Direct Cost: \43200000 )

  9. 造血器腫瘍に対する同種養子免疫療法の標的となるマイナー抗原の同定

    Grant number:17591025  2005.4 - 2007.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    赤塚美樹

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    Grant type:Competitive

    Grant amount:\3400000 ( Direct Cost: \3400000 )

  10. 日本人に頻度が高いHLAアリルにより拘束されるマイナー組織適合抗原の同定

    Grant number:15591035  2003.4 - 2005.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3400000 ( Direct Cost: \3400000 )

  11. マウスTL抗原を標的とした免疫療法モデルの開発(分担)

    Grant number:12217170  2001.4 - 2004.3

    日本学術振興会  科学研究費補助金  特定領域研究

    高橋 利忠、辻村 邦夫、赤塚美樹、中山 俊憲

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\66200000 ( Direct Cost: \66200000 )

  12. 血液細胞に特異的なマイナー組織適合抗原を標的とした白血病の免疫療法

    Grant number:13671092  2001.4 - 2003.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3400000 ( Direct Cost: \3400000 )

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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

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    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

    2018.4 - 2021.3 Fujita Health University)

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    Level:Undergraduate (specialized) 

  2. 血液内科学

    2018.4 - 2021.3 Fujita Health University)

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    Level:Undergraduate (specialized) 

  3. 薬物治療学

    2018.4 - 2020.3 Meijo University)

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    Level:Undergraduate (liberal arts) 

 

Social Contribution 3

  1. 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

  2. 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

  3. 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