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- Title
Combination with a Defucosylated Anti-HM1.24 Monoclonal Antibody plus Lenalidomide Induces Marked ADCC against Myeloma Cells and Their Progenitors.
- Authors
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
- Abstract
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.
- Subjects
MULTIPLE myeloma treatment; MONOCLONAL antibodies; CELL-mediated cytotoxicity; IMMUNOMODULATORS; THALIDOMIDE; PROGENITOR cells; GENE expression; DRUG resistance; CANCER cells
- Publication
PLoS ONE, 2013, Vol 8, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0083905