Hattori, Yutaka



Faculty of Pharmacy, Department of Pharmacy 病態生理学講座 (Shiba-Kyoritsu)



External Links

Career 【 Display / hide

  • 1984.04

    慶應義塾大学病院, 内科, 研修医

  • 1986.05

    川崎市立川崎病院, 内科, 医員

  • 1988.10

    国立がんセンター研究所, 分子腫瘍学部, 研究員

  • 1993.03

    Memorial Sloan-Kettering Cancer Center, Hematologic Oncology

  • 1996.05

    慶應義塾大学医学部内科学教室, 血液・感染・リウマチ内科, 助手

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Academic Background 【 Display / hide

  • 1978.04

    Keio University, School of Medicine

    University, Graduated

Academic Degrees 【 Display / hide

  • 医学博士, Keio University, 1991.02

    K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes.

Licenses and Qualifications 【 Display / hide

  • 医師免許, 1984.06

  • 日本内科学会認定内科医, 1987.12

  • 日本内科学会指導医, 2000.05

  • 日本血液学会認定血液専門医, 2004.10

  • 日本臨床腫瘍学会暫定指導医, 2005.09

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Books 【 Display / hide

  • フィジカルアセスメントに基づく症例解析と薬物治療

    青森達、大林恭子、齋藤義正、里美貴、須賀達夫、中村智徳、服部 豊、松下麻衣子, 京都廣川書店, 2021.08,  Page: 134

    Scope: 心不全の病態、慢性心不全の薬物治療,  Contact page: 10-14

  • 臨床薬学テキストシリーズ 血液・造血器/感染症/悪性腫瘍

    望月眞弓・加藤裕久・服部 豊, 中山書店, 2021.05,  Page: 395

    Scope: 修得すべき知識の概要、血液疾患の検査,  Contact page: 2,3,15-25

  • 多発性骨髄腫 新規治療薬の使い方・考え方

    HATTORI YUTAKA, 先端医学社(東京), 2017.06

    Scope: 開発中の薬剤 pp174-179

  • 骨髄腫治療を理解するためのMyeloma Biology

    HATTORI YUTAKA, 医薬ジャーナル社(大阪), 2017.05

    Scope: 肝細胞増殖因子(HGF)およびその受容体(c-MET) pp137-144

  • 悪性腫瘍の薬、病態、治療 スタンダード薬学シリーズ 医療薬学 IV.薬理、病態・薬物治療(4) 日本薬学会編

    服部 豊, 東京化学同人, 2017.04

    Scope: pp207-218

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Papers 【 Display / hide

  • SORT1/LAMP2-mediated Extracellular Vesicle Secretion and Cell Adhesion Are Linked to Lenalidomide Resistance in Multiple Myeloma

    Tomofumi Yamamoto, Jun Nakayama, Yusuke Yamamoto, Masahiko Kuroda, Yutaka Hattori, Takahiro Ochiya

    Blood Advance (American Society of Hematology)   2022.01

    Research paper (scientific journal), Accepted

  • Integrin β5 and β7 expression in lenalidomide-resistant multiple myeloma cells

    Yutaka Hattori · Takumi Futo · Ryo Uozaki · Daiju Ichikawa · Takashi Yamaguchi · Tomofumi Yamamoto · Maiko Matsushita · Maki Hirao

    International Journal of Hematology (Springer Nature)   2022

    Research paper (scientific journal), Joint Work, Accepted

  • Thermally-modulated cell separation columns using a thermoresponsive block copolymer brush as a packing material for the purification of mesenchymal stem cells

    Nagase K., Edatsune G., Nagata Y., Matsuda J., Ichikawa D., Yamada S., Hattori Y., Kanazawa H.

    Biomaterials Science (Biomaterials Science)  9 ( 21 ) 7054 - 7064 2021.11

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  20474830

     View Summary

    Cell therapy using mesenchymal stem cells (MSCs) is used as effective regenerative treatment. Cell therapy requires effective cell separation without cell modification and cellular activity reduction. In this study, we developed a temperature-modulated mesenchymal stem cell separation column. A temperature-responsive cationic block copolymer, poly(N,N-dimethylaminopropylacrylamide)-b-poly(N-isopropylacrylamide)(PDMAPAAm-b-PNIPAAm) brush with various cationic copolymer compositions, was grafted onto silica beads via two-step atom transfer radical polymerization. Using the packed beads, the elution behavior of the MSCs was observed. At 37 °C, the MSCs were adsorbed onto the column via both hydrophobic and electrostatic interactions with the PNIPAAm and PDMAPAAm segments of the copolymer brush, respectively. By reducing the temperature to 4 °C, the adsorbed MSCs were eluted from the column by reducing the hydrophobic and electrostatic interactions attributed to the hydration and extension of the PNIPAAm segment of the block copolymer brush. From the temperature-modulated adsorption and elution behavior of MSCs, a suitable DMAPAAm composition of the block copolymer brush was determined. Using the column, a mixture of MSC and BM-CD34+ cells was separated by simply changing the column temperature. The column was used to purify the MSCs, with purities of 78.2%, via a temperature change from 37 °C to 4 °C. Additionally, the cellular activity of the MSCs was retained throughout the column separation step. Overall, the obtained results show that the developed column is useful for MSC separation without cell modification and cellular activity reduction. This journal is

  • Antibody drug separation using thermoresponsive anionic polymer brush modified beads with optimised electrostatic and hydrophobic interactions

    Nagase K., Ishii S., Ikeda K., Yamada S., Ichikawa D., Akimoto A.M., Hattori Y., Kanazawa H.

    Scientific Reports (Nature Research)  10 ( 1 )  2020.12

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © 2020, The Author(s). Antibody drugs play an important role in biopharmaceuticals, because of the specificity for target biomolecules and reduction of side effects. Thus, separation and analysis techniques for these antibody drugs have increased in importance. In the present study, we develop functional chromatography matrices for antibody drug separation and analysis. Three types of polymers, poly(N-isopropylacrylamide (NIPAAm)-co-2-acrylamido-2-methylpropanesulfonic acid (AMPS)-co-N-phenyl acrylamide (PhAAm)), P(NIPAAm-co-AMPS-co-n-butyl methacrylate (BMA)), and P(NIPAAm-co-AMPS-co-tert-butylacrylamide (tBAAm)), were modified on silica beads through atom transfer radical polymerisation. Rituximab elution profiles were observed using the prepared beads-packed column. Rituximab adsorption at high temperature and elution at low temperature from the column were observed, as a result of the temperature-modulated electrostatic and hydrophobic interactions. Using the column, rituximab purification from contaminants was performed simply by changing the temperature. Additionally, three types of antibody drugs were separated using the column through temperature-modulated hydrophobic and electrostatic interactions. These results demonstrate that the temperature-responsive column can be applied for the separation and analysis of biopharmaceuticals through a simple control of the column temperature.

  • Characteristics of a novel target antigen against myeloma cells for immunotherapy

    Matsushita M., Saito S., Yokoe S., Ichikawa D., Hattori Y.

    Vaccines (MDPI)  8 ( 4 ) 1 - 13 2020.12

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Despite the availability of therapeutic treatments, multiple myeloma is an incurable haematological disorder. In this study, we aimed to clarify the role of CXorf48 as a therapeutic target in multiple myeloma. Based on a previously identified HLA-A*24:02-restiricted epitope from this novel cancer/testis antigen, we characterized the activities of cytotoxic T lymphocytes (CTLs) specific to this antigen against myeloma cells and evaluated the effects of demethylating agents in increasing antigen expression and enhancing the cytotoxic activity of CTLs. CXorf48 expression was examined by reverse transcription polymerase chain reaction (RT-PCR) using nine myeloma cell lines. Cell lines with low CXorf48 expression were treated by demethylating agents (DMAs), 5-azacytidine (5-aza), and 5-aza-2'-deoxycytidine (DAC) to evaluate gene expression using quantitative RT-PCR. Furthermore, CXorf48-specific CTLs were induced from peripheral blood mononuclear cells of HLA-A*24:02-positive healthy donors to evaluate antigen recognition using ELISpot and51 Cr cytotoxicity assays. CXorf48 was widely expressed in myeloma cells, and gene expression was significantly increased by DMAs. Furthermore, CXorf48-specific CTLs recognized DMA-treated myeloma cells. These findings suggest that CXorf48 is a useful target for immunotherapy, such as vaccination, in combination with demethylating agents for the treatment of patients with myeloma.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • Integrin β5 and β7 expression in lenalidomide-resistant multiple myeloma cells

    Hattori Y., Futo T., Uozaki R., Ichikawa D., Yamaguchi T., Yamamoto T., Matsushita M., Hirao M.

    International Journal of Hematology (International Journal of Hematology)  115 ( 4 ) 605 - 608 2022.04

    ISSN  09255710

  • Treatment of relapsed and refractory multiple myeloma

    Hisako Kunieda, Maki Hirao, Yutaka Hattori

    Hematological Malignancies (ver. 2) (Nihon Rinsho Co. Ltd)  78 ( 増刊号3 ) 638 - 644 2020.08

    Article, review, commentary, editorial, etc. (other), Joint Work

     View Summary

    Treatment strategies and regimen for relapsed or refractory multiple myeloma are summarized. Newly developed drugs or methods were also introduced.

  • A Challenge to Aging Society by microRNA in Extracellular Vesicles: microRNA in Extracellular Vesicles as Promising Biomarkers and Novel Therapeutic Targets in Multiple Myeloma.

    Yamamoto T, Kosaka N, Hattori Y, Ochiya T.

    J Clin Med. 7 ( 3 ) E55 2018.03

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

  • 下痢の受診勧奨のポイント


    日本薬剤師会雑誌 (日本薬剤師会)  67 ( 10 ) 1439 - 1441 2015

    Article, review, commentary, editorial, etc. (scientific journal), Single Work

  • 便秘の受診勧奨のポイント


    日本薬剤師会雑誌 (日本薬剤師会)  67 ( 7 ) 957 - 961 2015

    Article, review, commentary, editorial, etc. (scientific journal), Single Work

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Presentations 【 Display / hide

  • A novel candidate for immunological target in treatment of multiple myeloma.

    Matsushita M, Saito S, Mori K, Yokoe S, Ichikawa D, Hattori Y

    An AACR Special Conference on Tumor Immunology and Immunotherapy (Boston, U.S.A.) , 


    Poster presentation, American Association of Cancer Research

  • Dedifferentiation by reprogramming genes augmented drug resistance and clonal growth in myeloma cells

    Tsuji H, Futo T, Samata K, Yamamoto T, Ichikawa D, Matsushita M, Hattori Y

    81th annual meeting of the Japanese Society of Hematology (Tokyo) , 


    Poster presentation, Japanese Society of Hematology

  • Diverse molecular mechanisms of lenalidomide resistance in multiple myeloma cells

    Futo T, Uozaki R, Yamaguchi T, Yamamoto T, Tsuji H, Samata K, Ichikawa D, Matsushita M, Hattori Y

    81th Annual meeting of the Japanese Society of Hematology (Tokyo) , 


    Oral presentation (general), Japanese Society of Hematology

  • Novel compound derived from natural products, komaroviquinone, showed anti-myeloma activity in vivo

    Samata K, Okayama M, Fujimori K, Yamamoto T, Ichikawa D, Matsushita M, Suto Y, Iwasaki G, Yamada T, Hattori Y

    78th annual meeting of the Japanese cancer association, 


    Oral presentation (general)

  • 天然物由来成分komaroviquinone及びその誘導体群はin vivoにおいて抗骨髄腫活性を示す


    日本薬学会生物系薬学部会第20回Pharmaco-Hematologyシンポジウム (東京) , 


    Oral presentation (general), 日本薬学会生物系薬学部会

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 新たな概念によるハイリスク骨髄腫の予後不良に関わる分子機構の探索と克服薬の開発


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • ハイリスク造血器腫瘍の髄外病変に着目した新規ターゲットの探索と創薬研究


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • Drug discovery based on novel concept for overcoming high-risk myeloma which is still intractable despite of recent progress in the treatment


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

     View Summary

    Despite of the use of newly developed drugs, multiple myeloma (MM) with high-risk cytogenetic changes revealed significantly poor prognosis. Most patients acquired drug resistance and developed extra-medullary diseases.We found that N-cadherin and other mesenchymal genes were highly expressed in t(4;14)-positive high-risk MM patients, and E-cadherin and other epithelial genes were expressed in MM patients with normal karyotype. Those cadherin-positive MM cells demonstrated tumorigenicity to SCID mice.We also developed a new immunomudulatory drug (IMiDs), TC11, which showed anti-tumor activity via cereblon-independent pathway unlike previously developed IMiDs.In addition, we tried structural modification of TC11 and succeeded in significantly increasing water-solublity of TC11.

  • 難治性多発性骨髄腫に対する骨髄腫瘍血管新生を標的とした遺伝子治療法の開発と実践.


    慶應義塾大学, Keio Gijuku Academic Development Funds, Research grant, No Setting

  • 腫瘍血管新生を標的とした難治性多発性骨髄腫の新規治療法の開発と実践.


    財団法人 がん研究振興財団, 第35回がん研究助成金, Research grant, No Setting

Works 【 Display / hide

  • 教育上の業績




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    Direct contribution to education of clinical residents in the management of in & out-patients of Keio University Hospital.

Intellectual Property Rights, etc. 【 Display / hide

  • フェニルフタルイミド修飾体及びそれを有効成分とする抗癌剤

    Date applied: 2016-207402  2016.10 

    Patent, Joint

  • 化合物もしくはその薬理学的に許容される塩、抗腫瘍剤、又は活性酸素産生剤

    Date applied: 特願2016-031897  2016.02 

    Date published: 特開2017-149658  2017.08 

    Patent, Joint

  • ペプチド、樹状細胞、細胞傷害性T細胞、白血病ワクチン、及び白血病受動免疫療法剤

    Date applied: 特願2013-194119  2013.09 

    Date published: 特開2015-71543  2015.04 

    Date issued: 特許第6204130号  2017.09

    Patent, Joint

  • がん免疫療法

    Date applied: 特願2012-132288  2012.06 

    Date published: 特開2013-256454  2013.12 

    Date issued: 特許第5984113号  2016.08

    Patent, Joint

  • 多発性骨髄腫に伴う骨融解症状を診断するための診断剤及びその使用法.

    Date applied: P2011-17058  2011.01 

    Date published: 特開2012-159297  2012.08 

    Patent, Joint

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Awards 【 Display / hide

  • がん集学的治療研究財団第29回一般研究助成

    服部豊., 2008.12, がん集学的治療研究財団, サリドマイドを用いた多発性骨髄腫に対する自家造血幹細胞移植後の維持・強化療法.

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  • 日本白血病研究基金平成20年度一般研究賞

    服部豊., 2008.10, 日本白血病研究基金, 多発性骨髄腫の再発の分子機構とその克服.

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  • 高松宮妃癌研究癌研究基金研究助成受賞

    服部豊., 2008.01, 高松宮妃癌研究癌研究基金, 難治性造血器腫瘍に対するポストサリドマイド世代の画期的治療法の開発.

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  • がん集学的治療研究財団 第29回一般研究助成受賞


  • 日本白血病研究基金一般研究賞受賞


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Courses Taught 【 Display / hide











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Memberships in Academic Societies 【 Display / hide

  • The Pharmaceutical Society of Japan, 

  • The Japanese Society of Myeloma, 

  • American Society of Hematology, 

  • The Japanese Cancer Association, 

  • The Japanese Society of Hematology, 


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Committee Experiences 【 Display / hide

  • 2023.04

    president, The 48th Annual Meeting of the Japanese Society of Hematology

  • 2022.04

    Chairman, The pharmaceutical Society of Japan, the 22th Pharmaco-Hematology Symposium

  • 2005

    director, Japanese Society of Myeloma

  • 2000

    Editorial Board, Japanese Journal of Clinical Oncology

  • 1985

    Board of Councillors、Editorial provision committee , Japanese Society of Hematology