{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:37Z","timestamp":1792787617583,"version":"4.5.0"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["SFB-1479 \u2013 Project ID: 441891347"],"award-info":[{"award-number":["SFB-1479 \u2013 Project ID: 441891347"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"H2020 European Research Council","award":["\u00b0ERC-2022-ADG Project: 101094168 \u2014 AlloCure"],"award-info":[{"award-number":["\u00b0ERC-2022-ADG Project: 101094168 \u2014 AlloCure"]}],"id":[{"id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>The success of allogeneic hematopoietic cell transplantation (allo-HCT) is limited by acute graft-versus-host disease (aGVHD). We have previously reported that neutrophils can exacerbate tissue damage caused by conditioning regimens. Pegtarazimod is a synthetic peptide, derived from the capsid protein of human astrovirus serotype 1, that was shown to reduce neutrophil effector functions. Therefore, we evaluated the therapeutic activity of pegtarazimod against aGVHD. Pegtarazimod significantly reduced aGVHD-related mortality, histological aGVHD severity, and proinflammatory cytokines in multiple in vivo mouse models while maintaining the antileukemia effect. Mechanistically, pegtarazimod reduced inflammation by decreasing ROS production, as investigated using allo-HCT recipient mice with genetic inactivation of NADPH oxidase in the BM. In addition to the antiinflammatory effect, pegtarazimod protected intestinal organoids against TNF-induced toxicity and oxidative DNA damage. In the phase II clinical trial AURORA, pegtarazimod treatment was well tolerated in patients with corticosteroid-refractory aGVHD (ClinicalTrials.gov NCT06343792), with an overall response rate of 4\/7 patients at day 28. In summary, pegtarazimod reduced aGVHD in mice by suppressing proinflammatory neutrophil effector functions and preserving enterocyte integrity. The clinical trial data support tolerability of pegtarazimod in aGVHD patients, and further studies are needed to determine efficacy.<\/jats:p>","DOI":"10.1172\/jci205864","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:00:55Z","timestamp":1785859255000},"source":"Crossref","is-referenced-by-count":0,"title":["Pegtarazimod limits acute graft-versus-host disease mortality and severity in mice and is tolerated in patients"],"prefix":"10.1172","volume":"136","author":[{"given":"Verena","family":"Holzm\u00fcller","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"},{"name":"Spemann Graduate School of Biology and Medicine,"},{"name":"Faculty of Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Gawron","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"},{"name":"Faculty of Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Cathrin","family":"Burk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"},{"name":"Faculty of Biology,"},{"name":"German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and the Medical Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Verena","family":"Stell","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"},{"name":"Faculty of Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Sophia","family":"Baur","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"},{"name":"Spemann Graduate School of Biology and Medicine,"},{"name":"Faculty of Biology,"},{"name":"CIBSS \u2013 Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Z\u00e4hringer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Fetsch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"},{"name":"Faculty of Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"M\u00e4der","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Talvard-Balland","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neel","family":"Krishna","sequence":"additional","affiliation":[{"name":"ReAlta Life Sciences, Norfolk, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Cunnion","sequence":"additional","affiliation":[{"name":"ReAlta Life Sciences, Norfolk, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Thienel","sequence":"additional","affiliation":[{"name":"UT Partners, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Martini","sequence":"additional","affiliation":[{"name":"ReAlta Life Sciences, Norfolk, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Glenn","sequence":"additional","affiliation":[{"name":"ReAlta Life Sciences, Norfolk, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8595-3940","authenticated-orcid":true,"given":"James L.M.","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monzr M.","family":"Al Malki","sequence":"additional","affiliation":[{"name":"City of Hope National Medical Center, Duarte, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Choe","sequence":"additional","affiliation":[{"name":"Division of Hematology, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"P\u00e9rez-Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Roc\u00edo, Seville, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Schmitt-Graeff","sequence":"additional","affiliation":[{"name":"University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Buescher","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7502-0431","authenticated-orcid":true,"given":"Natalie","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"},{"name":"CIBSS \u2013 Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohreh","family":"Mansoori Moghadam","sequence":"additional","affiliation":[{"name":"Institute for Infection Control and Prevention and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Henneke","sequence":"additional","affiliation":[{"name":"CIBSS \u2013 Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany."},{"name":"Institute for Infection Control and Prevention and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffroy","family":"Andrieux","sequence":"additional","affiliation":[{"name":"Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-0602","authenticated-orcid":true,"given":"Melanie","family":"Boerries","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and the Medical Center, and"},{"name":"Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-3393","authenticated-orcid":true,"given":"Robert","family":"Zeiser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Medical Center, Faculty of Medicine,"},{"name":"German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and the Medical Center, and"},{"name":"CIBSS \u2013 Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2024.06.021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1609337"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-022-01741-3"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1917635"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3517"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-812891"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abp9675"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9454583"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0170203"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00558"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0132446"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2004.017178"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.10.006"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2242"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4484"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.105"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00163"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00508"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.05.003"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.3.751"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024025240"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900623"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2009.197434"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-55690-6"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005957"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-025-02586-2"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-198360"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2025031080"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170418"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.05.028"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi1501"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0909"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-019-0624-z"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123004"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2011170118"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.893659"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2019.03.010"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.65.10.38"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13154"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-011-0803-1"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130084"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6896"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.8.3250"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-44703-7"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.183"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3400"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20242180"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.12242"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-015-3828-3"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.03.020"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.242990"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.4161\/tisb.26938"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100948"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq431"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2024.100722"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-02014-7"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1139\/o59-099"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11010012"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/205864\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:01:43Z","timestamp":1790791303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/205864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":61,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,8,11]]},"published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1172\/JCI205864"],"URL":"https:\/\/doi.org\/10.1172\/jci205864","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"article-number":"e205864"}}