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

Biomolecules & Therapeutics 2021년 29권 2호 p.166 ~ 174
안재희, 이병현, 김성은, 권보은, 정현진, 최종립, 김민정, 박용, 김병수, 김대희, 고현정,
소속 상세정보
안재희 ( Ahn Jae-Hee ) - Kangwon National University College of Pharmacy
이병현 ( Lee Byung-Hyun ) - Kangwon National University Scripps Korea Antibody Institute
김성은 ( Kim Seong-Eun ) - Kangwon National University College of Pharmacy
권보은 ( Kwon Bo-Eun ) - Kangwon National University College of Pharmacy
정현진 ( Jeong Hyun-Jin ) - Kangwon National University College of Pharmacy
최종립 ( Choi Jong-Rip ) - Korea University College of Medicine Department of Internal Medicine
김민정 ( Kim Min-Jung ) - Korea University College of Medicine Department of Internal Medicine
박용 ( Park Yong ) - Kangwon National University Scripps Korea Antibody Institute
김병수 ( Kim Byung-Soo ) - Kangwon National University Scripps Korea Antibody Institute
김대희 ( Kim Dae-Hee ) - Korea University College of Medicine Department of Internal Medicine
고현정 ( Ko Hyun-Jeong ) - Kangwon National University College of Pharmacy

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.

키워드

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

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