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Responses of TLR7 to self-derived ssRNA have been implicated in the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). TLR7 antagonists and inhibitory anti-TLR7 monoclonal antibodies (mAbs) can protect lupus-prone NZBWF1 mice from lethal nephritis. However, less is known about TLR7 dependence and activation in human SLE, as both TLR7 and TLR8 respond to ssRNA in humans. Here, we analyzed public databases and found that TLR7 gene signature scores were consistently elevated across datasets, races, and SLEDAI scores compared to TLR8, suggesting a deeper involvement of TLR7 in SLE pathogenesis. To specifically inhibit human TLR7 responses, we developed inhibitory mAbs against human TLR7. Utilizing an inhibitory clone, we generated the humanized mAb, DS-7011a. DS-7011a effectively inhibited TLR7-mediated responses in plasmacytoid dendritic cells (pDCs) and B cells. Furthermore, DS-7011a was internalized in a TLR7-dependent manner and accumulated in B cells, pDCs, conventional dendritic cells (cDCs), and monocytes\/macrophages. In this study, we describe the generation and preclinical development of DS-7011a, which has the potential to be a therapeutic option for the treatment of SLE.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf046","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T14:19:57Z","timestamp":1757081997000},"page":"28-40","source":"Crossref","is-referenced-by-count":7,"title":["Anti-human TLR7 antibody for therapeutic intervention in systemic lupus erythematosus"],"prefix":"10.1093","volume":"38","author":[{"given":"Ryutaro","family":"Fukui","sequence":"first","affiliation":[{"name":"Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Synergy Institute for Futuristic Mucosal Vaccine Research and Development, Chiba University , Chiba ,","place":["Japan"]},{"name":"Medical Mycology Research Center, Chiba University , Chiba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Faculty of Pharmacy, Department of Pharmaceutical Sciences, Research Institute of Pharmaceutical Sciences, Musashino University , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuo","family":"Kanno","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Motoi","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Synergy Institute for Futuristic Mucosal Vaccine Research and Development, Chiba University , Chiba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Manno","sequence":"additional","affiliation":[{"name":"Discovery Research Laboratories II, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Honda","sequence":"additional","affiliation":[{"name":"Translational Science Department II, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinnosuke","family":"Yamada","sequence":"additional","affiliation":[{"name":"Translational Science Department II, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Discovery Research Laboratories V, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kagari","sequence":"additional","affiliation":[{"name":"Discovery Research Laboratories I, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Modality Research Laboratories II, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michinori","family":"Kadokura","sequence":"additional","affiliation":[{"name":"Modality Research Laboratories II, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Isobe","sequence":"additional","affiliation":[{"name":"Translational Research Laboratories, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Tomimori","sequence":"additional","affiliation":[{"name":"Translational Science, Daiichi Sankyo, Inc. , Basking Ridge, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Translational Science Department II, Daiichi Sankyo Co., Ltd. , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Senaldi","sequence":"additional","affiliation":[{"name":"Clinical Development, Daiichi Sankyo, Inc. , Basking Ridge, NJ 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