A novel anti-pd-l1 antibody exhibits antitumor effects on multiple myeloma in murine models via antibody-dependent cellular cytotoxicity

Jae Hee Ahn, Byung Hyun Lee, Seong Eun Kim, Bo Eun Kwon, Hyunjin Jeong, Jong Rip Choi, Min Jung Kim, Yong Park, Byung Soo Kim, Dae Hee Kim, Hyun Jeong Ko

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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 cyto-toxicity 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.

Original languageEnglish
Pages (from-to)166-174
Number of pages9
JournalBiomolecules and Therapeutics
Volume29
Issue number2
DOIs
Publication statusPublished - 2021
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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