Matsushita, Maiko

写真a

Affiliation

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

Position

Professor

External Links
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Career 【 Display / hide 】

  • 2000.04
    -
    2006.06

    慶応義塾大学医学部内科学教室助手

  • 2001.04
    -
    2004.03

    米国スローンケタリング記念癌研究所研究員

  • 2006.07
    -
    2010.03

    慶応義塾大学医学部先端医科学研究所助手

  • 2010.04
    -
    2014.03

    慶応義塾大学薬学部専任講師

  • 2015.04
    -
    Present

    慶應義塾大学薬学部准教授

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Academic Background 【 Display / hide 】

  • 1995.03

    Keio University, Faculty of Medicine

    University, Graduated

  • 2000.03

    Keio University, Graduate School, Division of Medicine

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 医学, Keio University, Coursework, 2001.10

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Research Areas 【 Display / hide 】

  • Life Science / Immunology

  • Life Science / General internal medicine (General Internal Medicine (includes Psychosomatic Medicine))

  • Life Science / Hematology and medical oncology

  • Oncology

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Research Themes 【 Display / hide 】

  • Development of novel immunotherapy against cancer, 

    2010.04
    -
    Present

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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

    大林恭子,中村智徳, 京都廣川書店, 2021.08

  • 臨床薬学テキストシリーズ　血液・造血器・感染症・悪性腫瘍

    乾賢一,望月眞弓,加藤裕久,服部豊, 中山書店, 2021.06,  Page： 28-35

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Papers 【 Display / hide 】

  • Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells

    Matsushita M., Kashiwazaki S., Kamiko S., Kobori M., Osada M., Kunieda H., Hirao M., Ichikawa D., Hattori Y.

    Pharmaceuticals (Pharmaceuticals)  16 ( 10 )  2023.10

    Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

    　View Summary

    Several anti-cancer drugs are known to have immunomodulatory effects, including immunogenic cell death (ICD) of cancer cells. ICD is a form of apoptosis which is caused by the release of damage-associated molecular patterns (DAMPs), the uptake of cancer antigens by dendritic cells, and the activation of acquired immunity against cancer cells. ICD was originally reported in solid tumors, and there have been few reports on ICD in multiple myeloma (MM). Here, we showed that proteasome inhibitors, including carfilzomib, induce ICD in myeloma cells via an unfolded protein response pathway distinct from that in solid tumors. Additionally, we demonstrated the potential impact of ICD on the survival of patients with myeloma. ICD induced by proteasome inhibitors is expected to improve the prognosis of MM patients not only by its cytotoxic effects, but also by building strong immune memory response against MM cells in combination with other therapies, such as chimeric antigen receptor—T cell therapy.

  • GTN057, a komaroviquinone derivative, induced myeloma cells' death in vivo and inhibited c-MET tyrosine kinase

    Okayama M., Fujimori K., Sato M., Samata K., Kurita K., Sugiyama H., Suto Y., Iwasaki G., Yamada T., Kiuchi F., Ichikawa D., Matsushita M., Hirao M., Kunieda H., Yamazaki K., Hattori Y.

    Cancer Medicine (Cancer Medicine)  12 ( 8 ) 9749 - 9759 2023.04

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    Objective: Despite the development of newly developed drugs, most multiple myeloma (MM) patients with high-risk cytogenetic abnormalities such as t(4;14) or del17p relapse at anin early stage of their clinical course. We previously reported that a natural product,komaroviquinone (KQN), isolated from the perennial semi-shrub Dracocephalum komarovi, i.e., komaroviquinone (KQN) and its derivative GTN024 induced the apoptosis of MM cells by producing reactive oxygen species (ROS), but both exhibited significant hematological toxicity. Aim of this study is to clarify anti-tumor activity, safety and pharmacokinetics of GTN057, an optimization compound of KQN in vivo. Methods: ICR/SCID xenograft model of KMS11, a t(4;14) translocation-positive MM cell line, was used for in vivo study. Mice pharmacokinetics of GTN057 and the degradation products were analyzed by LC-MS/MS. Results: Herein, our in vitro experiments revealed that GTN057 is much less toxic to normal hematopoietic cells, induced the apoptosis of both MM cell lines andpatient samples, including those with high-risk cytogenetic changes. A xenograft model of a high-risk MM cell line demonstrated that GTN057 significantly delayed the tumor growth with no apparent hematological or systemic toxicities in vivo. The pathological examination of GTN057-treated tumors in vivoshowed revealed apoptosis of MM cells and anti-angiogenesis. In addition to the production of ROS, GTN057 inhibited the downstream signaling of c-MET, a receptor tyrosine kinase a receptor forand hepatocyte growth factor (HGF) receptor. Thus, GTN057 is less toxic and is able tomay be a candidate drug for treating MM patients, via multifunctional mechanisms. We have also extensively studied the pharmacologyical analysis of GTN057. The metabolites of GTN057, (e.g.,such as GTN054), may also have anti-tumorantitumor activity. Conclusion: Natural products or and their derivatives can could be good sources of antineoplastic drugs even for high-risk cancer.

  • PAX5-positive plasma cell leukemia presenting as lymphocytosis

    Tateno S, Hirao M, Kikuchi T, Tsukada Y, Kunieda H, Osada M, Yamazaki K, Denda R, Hirose S, Matsushita M, Ichikawa D, Hattori Y.

    Rinsho Ketsueki (日本血液学会)  63 ( 10 ) 1415 - 1420 2022.11

    Research paper (scientific journal), Joint Work, Accepted

  • 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 115 ( 4 ) 605 - 608 2022.02

    Research paper (scientific journal), Joint Work, Accepted

  • Characteristics of a Novel Target Antigen Against Myeloma Cells for Immunotherapy

    Maiko Matsushita, Saku Saito, Shinya Yokoe, Daiju Ichikawa and Yutaka Hattori

    Vaccines (MDPI)  8 ( 4 ) 579 - 591 2020.10

    Research paper (scientific journal), Lead author, Corresponding author, 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 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 治療　抗がん剤

    服部　豊,松下　麻衣子

    日本医師会雑誌 (日本医師会)  151 ( 特別１ ) 125 - 130 2022.06

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

  • Novel treatment strategies utilizing immune reactions against chronic myelogenous leukemia stem cells

    Matsushita M

    Cancers (MDPI)  13 ( 21 ) 5435 2021.11

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

  • Immunogenic cell death in hematological malignancies.

    Matsushita M.

    臨床血液 (日本血液学会)  62 ( 7 ) 709 - 716 2021.07

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

  • Immunomodulatory effects of drugs for effective cancer immunotherapy.

    Matsushita M,Kawaguchi M.

    Journal of Oncology    ID 8653489 2018.10

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

  • Immunotherapy Targeting Leukemia Stem Cells.

    Matsushita M

    International Journal of Hematological Disorders (Science and Education Publishing)     39 - 42 2015.07

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

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Presentations 【 Display / hide 】

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

  • 去勢抵抗性前立腺癌に対する細胞外小胞スクリーニング法を用いた新規免疫増強薬の探索

    2024.04
    -
    2027.03

    基盤研究(C), Principal investigator

  • なぜ骨髄腫は治癒しないのか、分子病態の解明とオートファジー創薬による克服

    2023.04
    -
    2025.03

    文部科学省・日本学術振興会, 科学研究費助成事業, Research grant, Coinvestigator(s)

  • Development of novel combined immunotherapy using in silico screening system

    2018.04
    -
    2021.03

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

  • Development of novel immunotherapy targeting leukemic stem cells.

    2014.04
    -
    2017.03

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

    　View Summary

    Novel cancer antigen, CXorf48, was highly expressed in patients-derived leukemic stem cells. Cytotoxic T cells induced with HLA-A24-restricted epitope could recognize these leukemic stem cells from leukemic patients. We also found the correlation between existence of anti-CXorf48 CTL in peripheral blood of leukemic patients and their clinical courses.
    Moreover, demethylating agent up-regulated expression of CXorf48 gene in leukemic cells, but not in normal blood cells, suggesting that combination of demethylating agent with immunotherapy might be effective. Therefore, immnotherapy targeting CXorf48 would be a promising treatment for leukemia by eradicating leukemic stem cells.

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Intellectual Property Rights, etc. 【 Display / hide 】

  • 抗腫瘍剤(T 細胞受容体遺伝子導入Ｔ細胞)

    Date applied： 522741  2023.07 

    Patent, Joint

  • 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医薬組成物

    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： 2016-031897  2016.02 

    Date published： 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： 2013-194119  2013.09 

    Date announced： 2015-71543  2015.04 

    Date issued： 6204130  2017.09

    Date registered： 2017.09

    Patent, Joint

  • がん免疫療法

    Date applied： 2012-132288  2012.06 

    Date announced： 2013-256454(P2013-256454A)  2013.12 

    Date issued： 5984113  2016.08

    Patent, Joint

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Awards 【 Display / hide 】

  • 日本骨髄腫学会奨励賞

    松下麻衣子, 2015.05, 日本骨髄腫学会, 新規ホメオボックス蛋白由来抗原を用いた多発性骨髄腫に対する複合的免疫治療法の開発

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 日本白血病研究基金一般研究賞

    松下麻衣子, 2013.11, 日本白血病研究基金, 新規癌抗原を標的とした多発性骨髄腫に対する免疫治療法の開発

    Type of Award： Award from publisher, newspaper, foundation, etc.

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Courses Taught 【 Display / hide 】

  • STUDY OF MAJOR FIELD: (CLINICAL PHYSIOLOGY AND THERAPEUTICS)

    2025

  • SEMINAR: (CLINICAL PHYSIOLOGY AND THERAPEUTICS)

    2025

  • RESEARCH FOR BACHELOR'S THESIS 1

    2025

  • PRIOR LEARNING FOR CLINICAL PRACTICE 5

    2025

  • PRE-CLINICAL TRAINING FOR HOSPITAL & COMMUNITY PHARMACY

    2025

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