{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:36:16Z","timestamp":1791246976647,"version":"4.1.0"},"reference-count":62,"publisher":"American Society of Hematology","issue":"21","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,23]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Fanconi anemia (FA) is an inherited DNA repair disorder characterized by bone marrow (BM) failure, developmental abnormalities, myelodysplasia, leukemia, and solid tumor predisposition. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a mainstay treatment, is limited by conditioning regimen\u2013related toxicity and graft-versus-host disease (GVHD). Antibody-drug conjugates (ADCs) targeting hematopoietic stem cells (HSCs) can open marrow niches permitting donor stem cell alloengraftment. Here, we report that single dose anti-mouse CD45\u2013targeted ADC (CD45-ADC) facilitated stable, multilineage chimerism in 3 distinct FA mouse models representing 90% of FA complementation groups. CD45-ADC profoundly depleted host stem cell enriched Lineage\u2212Sca1+cKit+ cells within 48 hours. Fanca\u2212\/\u2212 recipients of minor-mismatched BM and single dose CD45-ADC had peripheral blood (PB) mean donor chimerism &amp;gt;90%; donor HSCs alloengraftment was verified in secondary recipients. In Fancc\u2212\/\u2212 and Fancg\u2212\/\u2212 recipients of fully allogeneic grafts, PB mean donor chimerism was 60% to 80% and 70% to 80%, respectively. The mean percent donor chimerism in BM and spleen mirrored PB results. CD45-ADC\u2013conditioned mice did not have clinical toxicity. A transient &amp;lt;2.5-fold increase in hepatocellular enzymes and mild-to-moderate histopathological changes were seen. Under GVHD allo-HSCT conditions, wild-type and Fanca\u2212\/\u2212 recipients of CD45-ADC had markedly reduced GVHD lethality compared with lethal irradiation. Moreover, single dose anti\u2013human CD45-ADC given to rhesus macaque nonhuman primates on days\u00a0\u22126 or\u00a0\u221210 was at least as myeloablative as lethal irradiation. These data suggest that CD45-ADC can potently promote donor alloengraftment and hematopoiesis without significant toxicity or severe GVHD, as seen with lethal irradiation, providing strong support for clinical trial considerations in highly vulnerable patients with FA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023023549","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T15:21:19Z","timestamp":1709738479000},"page":"2201-2216","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":13,"title":["Alloengraftment without significant toxicity or GVHD in CD45 antibody-drug conjugate\u2013conditioned Fanconi anemia mice"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4721-2695","authenticated-orcid":false,"given":"Asim","family":"Saha","sequence":"first","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Palchaudhuri","sequence":"additional","affiliation":[{"name":"2Magenta Therapeutics, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Lanieri","sequence":"additional","affiliation":[{"name":"2Magenta Therapeutics, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Hyzy","sequence":"additional","affiliation":[{"name":"2Magenta Therapeutics, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Riddle","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Panthera","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-2550","authenticated-orcid":false,"given":"Cindy R.","family":"Eide","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0957-4380","authenticated-orcid":false,"given":"Jakub","family":"Tolar","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Panoskaltsis-Mortari","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-2276","authenticated-orcid":false,"given":"Lev","family":"Gorfinkel","sequence":"additional","affiliation":[{"name":"3Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6011-0576","authenticated-orcid":false,"given":"Victor","family":"Tkachev","sequence":"additional","affiliation":[{"name":"4Massachusetts General Hospital Center for Transplantation Sciences, Mass General Brigham and Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Gerdemann","sequence":"additional","affiliation":[{"name":"3Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-8431","authenticated-orcid":false,"given":"Francesca","family":"Alvarez-Calderon","sequence":"additional","affiliation":[{"name":"3Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa Rojas","family":"Palato","sequence":"additional","affiliation":[{"name":"3Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret L.","family":"MacMillan","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Wagner","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie S.","family":"Kean","sequence":"additional","affiliation":[{"name":"3Boston Children's Hospital, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Osborn","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5949-4947","authenticated-orcid":false,"given":"Hans-Peter","family":"Kiem","sequence":"additional","affiliation":[{"name":"5Department of Medicine, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9821-7133","authenticated-orcid":false,"given":"David T.","family":"Scadden","sequence":"additional","affiliation":[{"name":"6Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA"},{"name":"7Harvard Stem Cell Institute, Cambridge, MA"},{"name":"8Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Olson","sequence":"additional","affiliation":[{"name":"2Magenta Therapeutics, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9608-9841","authenticated-orcid":false,"given":"Bruce R.","family":"Blazar","sequence":"additional","affiliation":[{"name":"1Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"1","key":"2024052315213791900_bib1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1097\/00062752-200301000-00011","article-title":"Genetic basis of Fanconi anemia","volume":"10","author":"Bagby","year":"2003","journal-title":"Curr Opin Hematol"},{"issue":"suppl 1","key":"2024052315213791900_bib2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1080\/10245330512331390096","article-title":"Fanconi anemia: current 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