Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity

  • Ahn, Jae-Hee (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Lee, Byung-Hyun (Scripps Korea Antibody Institute, Kangwon National University) ;
  • Kim, Seong-Eun (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Kwon, Bo-Eun (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Jeong, Hyunjin (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Choi, Jong Rip (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Kim, Min Jung (Department of Internal Medicine, Korea University College of Medicine) ;
  • Park, Yong (Scripps Korea Antibody Institute, Kangwon National University) ;
  • Kim, Byung Soo (Scripps Korea Antibody Institute, Kangwon National University) ;
  • Kim, Dae Hee (Department of Internal Medicine, Korea University College of Medicine) ;
  • Ko, Hyun-Jeong (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University)
  • Received : 2020.07.23
  • Accepted : 2020.10.05
  • Published : 2021.03.01
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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 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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References

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