Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors.
Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors.
复制标题
DOI：
10.1371/journal.pone.0083905
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Abe M
中科院分区：
文献类型：
--
作者：
Harada T;Ozaki S;Oda A;Tsuji D;Ikegame A;Iwasa M;Udaka K;Fujii S;Nakamura S;Miki H;Kagawa K;Kuroda Y;Kawai S;Itoh K;Yamada-Okabe H;Matsumoto T;Abe M
免疫调节药物来那度胺（lenalidomide, Len）引起了人们对增强抗体依赖性细胞毒性（ADCC）介导的免疫疗法的关注。我们开发了针对多发性骨髓瘤（MM）细胞中过表达的HM1.24 （CD317）的人源化单克隆抗体的去聚焦版本（YB-AHM）。在本研究中，我们通过YB-AHM和Len联合评估ADCC对MM细胞及其祖细胞的作用。YB-AHM能够通过ADCC选择性杀死低效靶比的MM患者骨髓样本中的MM细胞，Len治疗进一步增强了这一作用。有趣的是，Len也以效应依赖的方式上调MM细胞中HM1.24的表达。HM1.24在MM细胞耐药克隆“侧群”中高表达；在效应细胞存在的情况下，这种联合处理成功地降低了RPMI 8226和KMS-11细胞中的SP组分，并在集落形成实验中抑制了MM细胞的克隆生成潜力。综上所述，本研究提示YB-AHM和Len联合治疗可能成为MM的有效治疗策略，值得进一步研究以耐药MM克隆原细胞为靶点。
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.
登录
查看更多内容
影响因子：
2.1
作者：
Harada, Takeshi;Ozaki, Shuji;Abe, Masahiro
通讯作者：
Abe, Masahiro
影响因子：
5.2
作者：
Challen, GA;Little, MH
通讯作者：
Little, MH
影响因子：
20.3
作者：
Koene, HR;Kleijer, M;deHaas, M
通讯作者：
deHaas, M
DOI：
10.1006/bbrc.1999.0683
发表时间：
1999-05-19
影响因子：
3.1
作者：
Ohtomo, T;Sugamata, Y;Tsuchiya, M
通讯作者：
Tsuchiya, M
影响因子：
3.6
作者：
Ono, K;Ohtomo, T;Tsuchiya, M
通讯作者：
Tsuchiya, M