Combination of Defucosylated AHM plus Lenalidomide
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.
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.
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。
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/ )
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