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ID 106068
タイトル別表記
低フコース化抗HM1.24抗体とレナリドミドの併用は骨髄腫細胞および骨髄腫細胞幹細胞に著明なADCC活性を示す
Combination of Defucosylated AHM plus Lenalidomide
著者
原田, 武志 徳島大学大学院医科学教育部(医学専攻) 徳島大学 教育研究者総覧
尾崎, 修治 Tokushima Prefectural Central Hospital
Oda, Asuka University of Tokushima
池亀, 彰茂 Tokushima University
Iwasa, Masami University of Tokushima
Udaka, Kengo University of Tokushima
Kuroda, Yoshiaki Hiroshima University
Kawai, Shigeto Forerunner Pharma Research Co. Ltd.
Yamada-Okabe, Hisafumi Chugai Pharmaceutical Co. Ltd.
キーワード
Multiple myeloma
HM1.24
Lenalidomide
ADCC
資料タイプ
学位論文
抄録
The immunomodulatory drug lenalidomide (Len) has drawn attention to potentiate antibody-dependent cellular cytotoxicity (ADCC)-mediated immunotherapies. We developed the defucosylated version (YB-AHM) of humanized monoclonal antibody against HM1.24 (CD317) overexpressed in multiple myeloma (MM) cells. In this study, we evaluated ADCC by YB-AHM and Len in combination against MM cells and their progenitors. YB-AHM was able to selectively kill via ADCC MM cells in bone marrow samples from patients with MM with low effector/target ratios, which was further enhanced by treatment with Len. Interestingly, Len also up-regulated HM1.24 expression on MM cells in an effector-dependent manner. HM1.24 was found to be highly expressed in a drug-resistant clonogenic ‘‘side population’’ in MM cells; and this combinatory treatment successfully reduced SP fractions in RPMI 8226 and KMS-11 cells in the presence of effector cells, and suppressed a clonogenic potential of MM cells in colony-forming assays. Collectively, the present study suggests that YB-AHM and Len in combination may become an effective therapeutic strategy in MM, warranting further study to target drug-resistant MM clonogenic cells.
掲載誌名
PLOS ONE
ISSN
19326203
出版者
PLOS
8
12
開始ページ
e83905
発行日
2013-12-26
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201404221012.pdf
論文本文 : LID201405281001.pdf
本論文は, 著者Takeshi Haradaの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
Copyright: © 2013 Harada et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.( https://creativecommons.org/licenses/by/4.0/ )
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2668号
学位記番号
甲医第1188号
学位授与年月日
2014-03-24
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
薬学系
医学系
先端酵素学研究所