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.
Highlights
Multiple myeloma (MM) is characterized by the accumulation of neoplastic plasma cells in the bone marrow [1]
This result suggests that monoclonal antibody (mAb) against surface molecules commonly shared by MM cells and their progenitors are able to impair clonogenic MM cells or MM cancer stem cells (CSCs), MM CSCs are resistant to chemotherapeutic agents
We evaluated whether pretreatment of PBMCs with Len further enhances the antibody-dependent cellular cytotoxicity (ADCC) activity of YB-antiHM1.24 mAb (AHM)
Summary
Multiple myeloma (MM) is characterized by the accumulation of neoplastic plasma cells in the bone marrow [1]. We are currently focusing on the development of monoclonal antibody (mAb)-based immunotherapies that can target MM CSCs. Our recent study has shown that a small molecule antibody specific to human leukocyte antigen (HLA) class I can inhibit side population (SP) cells with the characteristics of CSCs in MM which express high levels of HLA [6]. Our recent study has shown that a small molecule antibody specific to human leukocyte antigen (HLA) class I can inhibit side population (SP) cells with the characteristics of CSCs in MM which express high levels of HLA [6] This result suggests that mAbs against surface molecules commonly shared by MM cells and their progenitors are able to impair clonogenic MM cells or MM CSCs, MM CSCs are resistant to chemotherapeutic agents
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
