Biomolecules & Therapeutics  https://doi.org/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
Jae-Hee Ahn1,†, Byung-Hyun Lee2,†, Seong-Eun Kim1, Bo-Eun Kwon1, Hyunjin Jeong1, Jong Rip Choi3, Min Jung Kim3, Yong Park2, Byung Soo Kim2, Dae Hee Kim3,* and Hyun-Jeong Ko1,4,*
1Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341,
2Scripps Korea Antibody Institute, Kangwon National University, Chuncheon 24341,
3Department of Internal Medicine, Korea University College of Medicine, Seoul 02841,
4Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea
*E-mail: kimdh1@gmail.com (Kim DH), hjko@kangwon.ac.kr (Ko HJ)
Tel: +82-33-250-8086 (Kim DH), +82-33-250-6923 (Ko HJ)
Fax: +82-33-250-8088 (Kim DH), +82-33-259-5631 (Ko HJ)
The first two authors contributed equally to this work.
Received: July 23, 2020; Revised: September 2, 2020; Accepted: October 5, 2020; Published online: November 3, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

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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 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.
Keywords: PD-L1, Multiple myeloma, Antibody-dependent cellular cytotoxicity (ADCC), Myeloid-derived suppressor cell (MDSC), Lenalidomide


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