期刊
BIOMOLECULES & THERAPEUTICS
卷 29, 期 2, 页码 166-174出版社
KOREAN SOC APPLIED PHARMACOLOGY
DOI: 10.4062/biomolther.2020.131
关键词
PD-L1; Multiple myeloma; Antibody-dependent cellular cytotoxicity (ADCC); Myeloid-derived suppressor cell (MDSC); Lenalidomide
资金
- Basic Science Research Program of the National Research Foundation of Korea (NRF) - Ministry of Science, ICT, and Future Planning [NRF-2017M3A9C8060387, NRF-2017M3A9C8060390]
- National Research Foundation of Korea [2017M3A9C8060390] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Multiple myeloma is a malignant cancer of plasma cells that remains incurable despite recent advancements in treatment. This study suggests that targeting the PD-L1 molecule with an anti-PD-L1 antibody could be a promising strategy for treating multiple myeloma, as it induces antibody-dependent cellular cytotoxicity against myeloma cells.
Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.
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