Biomol Ther.  2021 Mar;29(2):166-174. 10.4062/biomolther.2020.131.

A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity

Affiliations
  • 1Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
  • 2Scripps Korea Antibody Institute, Kangwon National University, Chuncheon 24341, Republic of Korea
  • 3Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea
  • 4Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea

Abstract

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 myeloidderived 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-PDL1 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.

Keyword

PD-L1; PD-L1; Multiple myeloma; Multiple myeloma; Antibody-dependent cellular cytotoxicity (ADCC); Antibody-dependent cellular cytotoxicity (ADCC); Myeloid-derived suppressor cell (MDSC); Myeloid-derived suppressor cell (MDSC); Lenalidomide; Lenalidomide
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