{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:21:27Z","timestamp":1792844487574,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Interstitial lung disease (ILD) is an important adverse event related to deruxtecan\u2010based antibody\u2010drug conjugates (DXd ADCs). Understanding mechanisms and translationally relevant preclinical models remain incompletely defined. Here, we established a reproducible cynomolgus monkey model of DXd ADC\u2010related ILD and performed the first integration of bronchoalveolar lavage fluid (BALF) extracellular vesicle (EV) proteomics with lung single\u2010cell RNA sequencing (scRNA\u2010seq). Weekly intravenous administration of a target\u2010nonbinding human IgG1 DXd ADC to cynomolgus monkeys for 12\u2009weeks consistently induced interstitial pneumonitis in all animals, with radiologic abnormalities emerging by Week 6 and progressing thereafter. Longitudinal SomaScan\u2010based proteomic analyses revealed a pronounced and selective increase in differentially expressed proteins (DEPs) in BALF\u2010derived EVs from Week 6 onward, exceeding changes observed in plasma or bulk BALF. Gene Ontology analysis showed enrichment of inflammatory, wound repair\/regeneration, and extracellular matrix remodeling pathways within the BALF EV compartment. Integration of BALF EV proteomics with lung scRNA\u2010seq demonstrated strong concordance between EV\u2010associated signatures and transcriptional programs in alveolar epithelial, mesenchymal, and immune cell populations. Core injury\u2010associated genes, including\n                    <jats:italic>FN1<\/jats:italic>\n                    ,\n                    <jats:italic>TIMP1<\/jats:italic>\n                    , and\n                    <jats:italic>COL3A1<\/jats:italic>\n                    , were broadly upregulated across cell types, along with cell\u2010type\u2010restricted signatures including AT1 cells (\n                    <jats:italic>BMP4<\/jats:italic>\n                    ,\n                    <jats:italic>HMOX2<\/jats:italic>\n                    ), AT2 cells (\n                    <jats:italic>CXCL2<\/jats:italic>\n                    ,\n                    <jats:italic>SIRPA<\/jats:italic>\n                    ), fibroblasts (\n                    <jats:italic>TNC<\/jats:italic>\n                    ,\n                    <jats:italic>IGF1<\/jats:italic>\n                    ), endothelial cells (\n                    <jats:italic>LCP1<\/jats:italic>\n                    ,\n                    <jats:italic>CXCL12<\/jats:italic>\n                    ), neutrophils (\n                    <jats:italic>ADAM17<\/jats:italic>\n                    ), and macrophages (\n                    <jats:italic>CD84, HAVCR2<\/jats:italic>\n                    ,\n                    <jats:italic>CXCL10<\/jats:italic>\n                    ). Together, this study defines a robust cynomolgus monkey model of DXd ADC\u2010related ILD and identifies BALF EVs as a sensitive, lung\u2010localized molecular readout and a promising translational source of mechanistic insights.\n                  <\/jats:p>","DOI":"10.1111\/cas.70424","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T12:21:29Z","timestamp":1779711689000},"page":"2305-2316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pathophysiological and Molecular Features of\n                    <scp>DXd ADC<\/scp>\n                    \u2010Related Interstitial Pneumonitis in Cynomolgus Monkeys"],"prefix":"10.1111","volume":"117","author":[{"given":"Kazuyoshi","family":"Kumagai","sequence":"first","affiliation":[{"name":"Medicinal Safety Research Laboratories Daiichi Sankyo Co., Ltd.  Tokyo Japan"},{"name":"Medicinal Safety Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Medicinal Safety Research Laboratories Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Kubota","sequence":"additional","affiliation":[{"name":"Medicinal Safety Research Laboratories Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Medicinal Safety Research Laboratories Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Medicinal Safety Research Laboratories Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Chiba","sequence":"additional","affiliation":[{"name":"Medicinal Safety Research Laboratories Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-13-39"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.68.2005"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100404"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7100356"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.02.020"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2023.102043"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-24-01544"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03885-3"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2822"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0206"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1745"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0554"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-23-0287"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14686"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-01423-y"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14344-7"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11010087"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026332"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-87183-2_4"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33160-9"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0127-2023"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0106-2021"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115696"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-022-00210-0"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.168889"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.005"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009990"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2018-0062OC"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-025-03330-6"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-025-03181-1"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11203318"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00197"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073651"},{"issue":"12","key":"e_1_2_13_35_1","article-title":"Extracellular 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