Matsushita, Maiko



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


Associate Professor

External Links

Career 【 Display / hide

  • 2000.04


  • 2001.04


  • 2006.07


  • 2010.04


  • 2015.04


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

Academic Degrees 【 Display / hide

  • 医学, Keio University, Coursework, 2001.10


Research Areas 【 Display / hide

  • Immunology

  • General internal medicine (including psychosomatic medicine) (General Internal Medicine (includes Psychosomatic Medicine))

  • Hematology

  • Oncology

Research Themes 【 Display / hide

  • Development of novel immunotherapy against cancer, 



Papers 【 Display / hide

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

    Matsushita M.

    Cancers (MDPI)  13 ( 21 )  2021.11

    Research paper (scientific journal), Single Work, Accepted

     View Summary

    Introduction of tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myelogenous leukemia (CML), and treatment-free remission (TFR) is now a treatment goal. However, about half of the patients experience molecular relapse after cessation of TKIs, suggesting that leukemic stem cells (LSCs) are resistant to TKIs. Eradication of the remaining LSCs using immunotherapies including interferon-alpha, vaccinations, CAR-T cells, and other drugs would be a key strategy to achieve TFR.

  • 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

    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.

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

Reviews, Commentaries, etc. 【 Display / hide

  • Immunomodulatory effects of drugs for effective cancer immunotherapy.

    Matsushita M,Kawaguchi M.

    Journal of Oncology    ID 8653489 2018.10

    Introduction and explanation (scientific journal), Joint Work

  • Immunotherapy Targeting Leukemia Stem Cells.

    Matsushita M

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

    Introduction and explanation (scientific journal), Single Work

  • 造血器腫瘍における免疫療法.


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

    Introduction and explanation (commerce magazine), Single Work

  • がん幹細胞を標的とした免疫療法.

    河上裕, 松下麻衣子, 植田良, 塚本信夫, 大多茂樹.

    日本臨牀 (日本臨牀)  70(12)   p2142-2146 2012.12

    Introduction and explanation (commerce magazine), Joint Work

  • Quantitative analysis of PRAME for detection of minimal residual disease in leukemia.

    Matsushita M*, Yamazaki R, Kawakami Y.

    Methods Mol Med (Human Press Inc.)  97   267-275 2004.02

    Introduction and explanation (scientific journal), Joint Work

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Presentations 【 Display / hide

  • 前立腺癌幹細胞を標的とした免疫療法の基礎的検討


    第18回日本免疫治療学会学術集会, 2021.05, Poster (general)

  • 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 (general)

  • 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 report,etc., 日本血液学会

  • 多発性骨髄腫細胞のレナリドミド耐性に関する多様な分子メカニズム

    不藤拓海、宇於崎 凉, 山口 高史, 山元 智史, 辻 宏樹, 佐俣 光一, 市川 大, 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, Oral Presentation(general), 日本血液学会

  • komaroviquinoneという天然物由来の新規化合物がin vivoにおいて抗MM活性を示す


    第78回日本癌学会学術総会 (京都) , 2019.09, Oral Presentation(general)

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

  • Development of novel combined immunotherapy using in silico screening system


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 松下 麻衣子, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • Development of novel immunotherapy targeting leukemic stem cells.


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 松下 麻衣子, 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.

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

    Application No.: 2016-207402  2016.10 

    Patent, Joint, National application

  • 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

    Application No.: 2016-031897  2016.02 

    Publication No.: 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

    Application No.: 2013-194119  2013.09 

    Announcement No.: 2015-71543  2015.04 

    Registration No.: 6204130  2017.09

    Patent, Joint, National application

  • がん免疫療法

    Application No.: 2012-132288  2012.06 

    Announcement No.: 2013-256454(P2013-256454A)  2013.12 

    Registration No.: 5984113  2016.08

    Patent, Joint, National application

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: Awards of National Conference, Council and Symposium

  • 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: Awards of Publisher, Newspaper Company and Foundation


Courses Taught 【 Display / hide











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