Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors

• Material Type: 博士論文
• Title: Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors
• Author/Editor: Harada, Takeshi; Ozaki, Shuji; Oda, Asuka; Tsuji, Daisuke; Ikegame, Akishige; Iwasa, Masami; Udaka, Kengo; Fujii, Shiro; Nakamura, Shingen; Miki, Hirokazu; Kagawa, Kumiko; Kuroda, Yoshiaki; Kawai, Shigeto; Itoh, Kohji; Yamada-Okabe, Hisafumi; Matsumoto, Toshio; Abe, Masahiro
• Author Heading: Harada, Takeshi; Ozaki, Shuji; Oda, Asuka; Tsuji, Daisuke; Ikegame, Akishige; Iwasa, Masami; Udaka, Kengo; Fujii, Shiro; Nakamura, Shingen; Miki, Hirokazu; Kagawa, Kumiko; Kuroda, Yoshiaki; Kawai, Shigeto; Itoh, Kohji; Yamada-Okabe, Hisafumi; Matsumoto, Toshio; Abe, Masahiro
• Publication, Distribution, etc.: PLOS
• Publication Date: 2013-12-26
• Publication Date (W3CDTF): 2013-12-26
• Alternative Title: 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
• Periodical title: PLOS ONE
• No. or year of volume/issue: 8 12
• Volume: 8
• Issue: 12
• Pages: e83905-
• ISSN (Periodical Title): ISSN : 1932-6203
• Degree grantor/type: 徳島大学
• Date Granted: 2014-03-24
• Dissertation Number: 甲第2668号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Multiple myeloma; HM1.24; Lenalidomide; ADCC
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): 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/ )
• Related Material (DOI): 10.1371/journal.pone.0083905
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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