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dc.contributor.authorChapuis, Aude G
dc.contributor.authorEgan, Daniel N
dc.contributor.authorBar, Merav
dc.contributor.authorSchmitt, Thomas M
dc.contributor.authorMcAfee, Megan S
dc.contributor.authorPaulson, Kelly G
dc.contributor.authorVoillet, Valentin
dc.contributor.authorGottardo, Raphael
dc.contributor.authorRagnarsson, Gunnar B
dc.contributor.authorBleakley, Marie
dc.contributor.authorYeung, Cecilia C
dc.contributor.authorMuhlhauser, Petri
dc.contributor.authorNguyen, Hieu N
dc.contributor.authorKropp, Lara A
dc.contributor.authorCastelli, Luca
dc.contributor.authorWagener, Felecia
dc.contributor.authorHunter, Daniel
dc.contributor.authorLindberg, Marcus
dc.contributor.authorCohen, Kristen
dc.contributor.authorSeese, Aaron
dc.contributor.authorMcElrath, M Juliana
dc.contributor.authorDuerkopp, Natalie
dc.contributor.authorGooley, Ted A
dc.contributor.authorGreenberg, Philip D
dc.date.accessioned2019-09-13T15:35:47Z
dc.date.available2019-09-13T15:35:47Z
dc.date.issued2019-07
dc.date.submitted2019-09-13
dc.identifier.citationT cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. 2019, 25(7):1064-1072 Nat Meden_US
dc.identifier.issn1546-170X
dc.identifier.pmid31235963
dc.identifier.doi10.1038/s41591-019-0472-9
dc.identifier.urihttp://hdl.handle.net/2336/621044
dc.descriptionTo access publisher's full text version of this article click on the hyperlink belowen_US
dc.description.abstractRelapse after allogeneic hematopoietic cell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) entering HCT with poor-risk features1-3. When HCT does produce prolonged relapse-free survival, it commonly reflects graft-versus-leukemia effects mediated by donor T cells reactive with antigens on leukemic cells4. As graft T cells have not been selected for leukemia specificity and frequently recognize proteins expressed by many normal host tissues, graft-versus-leukemia effects are often accompanied by morbidity and mortality from graft-versus-host disease5. Thus, AML relapse risk might be more effectively reduced with T cells expressing receptors (TCRs) that target selected AML antigens6. We therefore isolated a high-affinity Wilms' Tumor Antigen 1-specific TCR (TCRC4) from HLA-A2+ normal donor repertoires, inserted TCRC4 into Epstein-Bar virus-specific donor CD8+ T cells (TTCR-C4) to minimize graft-versus-host disease risk and enhance transferred T cell survival7,8, and infused these cells prophylactically post-HCT into 12 patients ( NCT01640301 ). Relapse-free survival was 100% at a median of 44 months following infusion, while a concurrent comparative group of 88 patients with similar risk AML had 54% relapse-free survival (P = 0.002). TTCR-C4 maintained TCRC4 expression, persisted long-term and were polyfunctional. This strategy appears promising for preventing AML recurrence in individuals at increased risk of post-HCT relapse.en_US
dc.description.sponsorshipJuno Therapeutics Immunotherapy Integrated Research Center at the Fred Hutchinson Cancer Research Center Damon Runyon Guillot Family ZachAttacksLeukemia Foundationen_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.urlhttps://www.nature.com/articles/s41591-019-0472-9en_US
dc.subjectBráðahvítblæðien_US
dc.subjectStofnfrumuígræðslaen_US
dc.subject.meshLeukemia, Myeloid, Acuteen_US
dc.subject.meshHematopoietic Stem Cell Transplantationen_US
dc.titleT cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.en_US
dc.typeArticleen_US
dc.contributor.department1 Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 2 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 3 University of Washington School of Medicine, Seattle, WA, USA. 4 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 5 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 6 Landspítali Háskólasjúkrahús, Reykjavík, Iceland. 7 Alpine Biotech, Seattle, WA, USA. 8 Therapeutic Products Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 9 School of Informatics, University of Edinburgh, Edinburgh, UK. 10 Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. pgreen@u.washington.edu. 11 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. pgreen@u.washington.edu. 12 University of Washington School of Medicine, Seattle, WA, USA. pgreen@u.washington.edu. 13 Departments of Immunology and Medicine, University of Washington, Seattle, WA, USA. pgreen@u.washington.edu.en_US
dc.identifier.journalNature Medicineen_US
dc.rights.accessLandspitali Access - LSH-aðganguren_US
dc.departmentcodeMAO12
dc.source.journaltitleNature medicine


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