2018 Fiscal Year Final Research Report
Development of a specific antibody therapy for newly identified CD34 antigen-negative leukemic stem cell niche
| Project/Area Number |
16K09861
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
薗田 精昭 関西医科大学, 医学部, 客員教授 (60206688)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 白血病 / 抗体療法 |
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| Outline of Final Research Achievements |
It has been thought that leukemic stem cells (LSCs) resided in CD34+CD38- population as normal hematopoietic cells (HSCs) did so. But, as we identified more undifferentiated HSCs in CD34- population, we also identified more undifferentiated CD34-leukemic stem cells than CD34+CD38- LSCs.
We showed scid-repopulating capacity of CD34- LSCs and produced antibodies by immunizing mice with CD34- LSCs which were able to repopulate mice. Among these antibodies, antigen of a clone 303-23 was identified as antigen-X which was known as a target of a lot of kinds of solid tumor. Administration of the antibody had an effect to leukemic cells transplanted into mice.
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| Free Research Field |
白血病に対する免疫療法
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| Academic Significance and Societal Importance of the Research Achievements |
白血病に対する治療は進歩を遂げているものの、難治例や再発例は決して少なくなく、未だ難治性の疾患であることには変わりがない。白血病の再発はごく少数体内（骨髄内）に存在する白血病幹細胞が抗がん剤に対する非常に高い耐性を持っているからだと言われている。我々は従来の白血病幹細胞の概念よりもよりさらに根幹に存在する新規の白血病幹細胞＝CD34陰性白血病幹細胞が存在することを見出した。白血病に治療成績を向上させるために、このCD34陰性白血病幹細胞に対する抗体を作製することに成功し、実際に実験によって白血病に対する効果を認めている。さらに臨床応用にむけて、新規抗体療法の開発を継続する予定である。
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