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Monoclonal antibody Daratumumab promotes macrophage-mediated anti-myeloma phagocytic activity via engaging FC gamma receptor and activation of macrophages

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Abstract

Daratumumab (DAR) is novel human anti-CD38 IgG1, high-affinity human monoclonal antibody having broad-spectrum killing activity. The antibody is recommended to treat multiple myeloma. Recently Antibody-dependent cellular phagocytosis (ADCP) have been identified as the potential mechanism of DAR in addition to complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). In the present study we evaluated the effect of Daratumumab on other effector cells of multiple myeloma. Luciferase+ MM.1R GFP cells were selected for the study. For immune-compromised multiple myeloma tumour xenograft mouse model we used severe combined immunodeficient beige (SCID-beige), NOD SCID gamma (NSG) and C57Bl/6j mice. Bioluminescence imaging was carried by injecting luciferin, and in vivo confocal microscopy was done for tracing bone marrow niches. Spleen and tumours were submitted to immunophenotypic analysis. MTT assay was done for cell proliferation studies. We established tumour xenograft mouse model. It was found that DAR showed significant anti-tumour effect in tumour xenograft multiple myeloma mice. We found that DAR showed anti-tumour activity via Fc–FcγR interaction with macrophages. DAR induced phenotypic activation of macrophages in mice and resulted in ADCP of cancerous cells via interacting Fc-FcγR in vitro. The study suggested that DAR exerted anti-tumour activity in multiple myeloma by interacting with Fc-FcγR.

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Acknowledgements

The authors are grateful to the staff and management of Shaanxi Provincial People’s Hospital, China for providing necessary facilities. The authors express special thanks to all the funding agencies ‘Xian Foundation for Development of Science and Technology, China (Grant No. 20YXYJ0009 (11)), Science and Technology Talents Project of Shaanxi provincial of people's hospital ,China (Grant No. 2021BJ-26), SPPH incubator fund for Development of Science and Technology (Grant No. 2021YJY-19) and International Science and Technology Cooperation Projects of Shaanxi (Grant No.2022KW-14)’ for providing the necessary financial support.

Funding

This study was supported by Xian Foundation for Development of Science and Technology, China (Grant No. 20YXYJ0009 (11)).

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  1. Ying Gao and Lan Li both have contributed equally to this work.

Authors and Affiliations

  1. Department of Infectious Diseases, Shaanxi Provincial People’s Hospital, The Affiliated Hospital of Xi’an Medical University, 256 West Youyi Road, Xi’an, 710068, China

    Ying Gao, Lan Li, Yan Zheng, Weihua Zhang, Ben Niu & Yu Li

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  1. Ying Gao
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  2. Lan Li
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  3. Yan Zheng
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Contributions

YG and YL designed the concept and study; LL, YZ, WZ and BN along with YG and YL designed the experiments and performed them as a team. All the authors contributed equally to writing of the manuscript.

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Correspondence to Yu Li.

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The authors declare no conflict of interest.

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The animal protocols were approved by the animal ethical review committee of Shaanxi Provincial Peoples Hospital, China (approval number SP003V). The animal studies were in accordance to Guidelines for the ethical review of laboratory animal welfare People’s Republic of China National Standard GB/T 35892–2018 guidelines.

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Gao, Y., Li, L., Zheng, Y. et al. Monoclonal antibody Daratumumab promotes macrophage-mediated anti-myeloma phagocytic activity via engaging FC gamma receptor and activation of macrophages. Mol Cell Biochem 477, 2015–2024 (2022). https://doi.org/10.1007/s11010-022-04390-8

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