Matsushita, Maiko

写真a

Affiliation

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

Position

Associate 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 】

  • 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), 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.

  • A Study on the Description of Anticancer Drug Combination Therapy in Package Insert

    Shibata S, Matsushita M, Tsukamoto K, Chiba K, Ozaki K, Suzuki T

    BPB Reports （The Pharmaceutical Society of Japan)  3 （ 5 ） 157 - 165 2020.10

    Research paper (scientific journal), Joint Work, Accepted

  • Detection of residual disease in chronic myeloid leukemia utilizing genomic next generation sequencing reveals persistence of differentiated Ph<sup>+</sup> B cells but not bone marrow stem/progenitors

    Karigane D., Kasahara H., Shiroshita K., Fujita S., Kobayashi H., Tamaki S., Yamazaki R., Yahagi K., Yatabe Y., Kondoh N., Arai T., Katagiri H., Shimizu N., Sakurai M., Kikuchi T., Kato J., Shimizu T., Hayakawa T., Yaguchi T., Matsushita M., Nakajima H., Kawakami Y., Murata M., Mori T., Sasaki T., Okamoto S., Takubo K.

    Leukemia and Lymphoma （Taylor & Francis)  62 （ 3 ） 679 - 687 2020.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  10428194

    　View Summary

    © 2020 Informa UK Limited, trading as Taylor & Francis Group. Persistence of leukemic stem cells (LSCs) results in the recurrence of chronic myeloid leukemia (CML) after the administration of tyrosine kinase inhibitors (TKIs). Thus, the detection of minimal residual disease (MRD) with LSC potential can improve prognosis. Here, we analyzed 115 CML patients and found that CD25 was preferentially expressed on the phenotypic stem and progenitor cells (SPCs), and TKI therapy decreased the number of CD25-positive cells in the SPC fraction. To detect MRD harboring BCR-ABL1 fusion DNA, we developed a highly-sensitive method using patient-specific primers and next-generation sequencing. By using this method, we identified that in patients who achieved molecular remission, almost all residual CD25-positive SPCs were BCR-ABL1-negative. Moreover, in some patients BCR-ABL1 was detectable in peripheral B cells but not in SPCs. We conclude that CD25 marks LSCs at diagnosis but does not mark MRD following TKI treatment and that analysis of peripheral B cells can allow sensitive detection of MRD.

  • A phenylphthalimide derivative, TC11, induces apoptosis by degrading MCL1 in multiple myeloma cells

    Ichikawa D., Nakamura M., Murota W., Osawa S., Matsushita M., Yanagawa H., Hattori Y.

    Biochemical and Biophysical Research Communications （ELSEVIER)  521 （ 1 ） 252 - 258 2020.01

    Research paper (scientific journal), Accepted,  ISSN  0006291X

    　View Summary

    © 2019 To date, the prognosis of multiple myeloma (MM) in patients harboring cytogenetic abnormalities (CA) involving t (4; 14) and deletion of chromosome 17 remains poor despite recent advances in drug development that include the use of immunomodulatory drugs (IMiDs) such as lenalidomide for MM. To address this issue, we have developed a novel phenylphthalimide derivative, TC11, that is structurally related to IMiDs. It remains unclear how TC11 induces apoptosis of MM cells with high-risk CA. Here, we show that TC11 does not induce degradation of CRBN's substrates, IKZF1/3 and CK1α, and induces apoptosis of CRBN-silenced MM; this effect was independent of the cereblon (CRBN) pathway, which is involved in the mechanism of action of IMiDs used for the treatment of MM. We also revealed that TC11, in contrast to existing IMiDs, induced degradation of MCL1 and activation of caspase-9. Furthermore, inhibition of CDK1 by CGP74514A prevented TC11-induced MCL1 degradation, caspase-9 activation, and the subsequent apoptotic cell death. We showed that ectopic MCL1 expression rescued apoptosis of MM. These observations suggest that TC11 induces apoptotic death caused by degradation of MCL1 during prolonged mitotic arrest. Therefore, our findings suggest that TC11 is a potential drug candidate for high-risk MM.

  • A novel derivative (GTN024) from a natural product, komaroviquinone, induced the apoptosis of high-risk myeloma cells via reactive oxygen production and ER stress.

    Okayama M, Kitabatake S, Sato M, Fujimori K, Ichikawa D, Matsushita M, Suto Y, Iwasaki G, Yamada T, Kiuchi F, Hirao M, Kunieda H, Osada M, Okamoto S, Hattori Y

    Biochem Biophys Res Commun （Biochemical and Biophysical Research Communications)  505 （ 3 ） 787 - 793 2018.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0006291X

    　View Summary

    © 2018 Elsevier Inc. New drugs have significantly improved the survival of patients with multiple myeloma (MM), but the prognosis of MM patients with high-risk cytogenetic changes such as t(4; 14), t(14; 16) or del17p remains very poor. A natural product, komaroviquinone (KQN), was originally isolated from the perennial semi-shrub Dracocephalum komarovi and has anti-protozoal activity against Trypanosoma cruzi, the organism causing Chagas’ disease. Here we demonstrate that a novel KQN-derivative, GTN024, has an anti-MM effect both in vitro and in vivo. GTN024 induced the apoptosis of MM cell lines including those with high-risk cytogenetic changes. GTN024 produced reactive oxygen species (ROS) and increased phosphorylated eIF2α. The ROS production and subsequent endoplasmic reticulum (ER) stress are thought to play a key role in GTN024-induced apoptosis, as the apoptosis was completely abrogated by anti-oxidant treatment. In a mouse xenograft model, an intraperitoneal injection of 20 mg/kg of GTN024 significantly delayed tumor growth. Hematological toxicity and systemic toxicity as indicated by weight loss were not observed. These results suggest that the novel KQN-derivative GTN024 could become a candidate drug for treating high-risk MM.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 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

  • 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

  • 造血器腫瘍における免疫療法.

    松下麻衣子.

    産科と婦人科 (診断と治療社)  81(2)   217-222 2014.02

    Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Single Work

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Presentations 【 Display / hide 】

  • 既存の多発性骨髄腫治療薬がオートファジー経路に及ぼす影響

    Ryo Kaneko, Daiju Ichikawa, Maiko Matsushita, Yutaka Hattori

    2021.09
    -
    2021.10
    , 

    Poster presentation

  • 多発性骨髄腫における免疫原生細胞死に寄与するシグナル経路の検討

    Yuta Shimizu, Daiju Ichikawa, Maiko Matsushita, Yutaka Hattori

    第46回日本骨髄腫学会学術集会, 

    2021.05
    , 

    Poster presentation

  • 前立腺癌幹細胞を標的とした免疫療法の基礎的検討

    松下麻衣子,清水湧太,田中洸太郎,須田ゆきの,横江信哉,小坂威雄,大家基嗣,市川大樹,服部豊

    第18回日本免疫治療学会学術集会, 

    2021.05
    , 

    Poster presentation

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

    Maiko Matsushita, Saku Saito, Kanae Mori, Shinya Yokoe, Daiju Ichikawa, Yutaka Hattori

    An AACR Special Conference on Tumor Immunology and Immunotherapy, 

    2019.11
    , 

    Poster presentation

  • 骨髄腫細胞においてリプログラミング遺伝子による脱分化が薬剤抵抗性とクローン増殖性を増強する

    辻宏樹,不藤 拓海, 佐俣 光一, 山元 智史, 市川 大樹, 松下 麻衣子, 服部 豊

    第81回日本血液学会学術集会 (東京) , 

    2019.10
    , 

    Media coverage, 日本血液学会

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

  • 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 】

  • 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

    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 】

  • BACHELOR'S THESIS

    2022

  • ADVANCED PHARMACOTHERAPY

    2022

  • ADVANCED MOLECULAR BIOLOGY OF DISEASE

    2022

  • BIOTECH-DISCOVERY-BASED MEDICINE AND GENOME INFORMATICS

    2022

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

    2022

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