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Chapuis, Aude G; Egan, Daniel N; Bar, Merav; Schmitt, Thomas M; McAfee, Megan S; Paulson, Kelly G; Voillet, Valentin; Gottardo, Raphael; Ragnarsson, Gunnar B; Bleakley, Marie; Yeung, Cecilia C; Muhlhauser, Petri; Nguyen, Hieu N; Kropp, Lara A; Castelli, Luca; Wagener, Felecia; Hunter, Daniel; Lindberg, Marcus; Cohen, Kristen; Seese, Aaron; McElrath, M Juliana; Duerkopp, Natalie; Gooley, Ted A; Greenberg, Philip D
Nature medicine, 07/2019, Letnik: 25, Številka: 7Journal Article
Relapse after allogeneic hematopoietic cell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) entering HCT with poor-risk features . 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 cells . 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 disease . Thus, AML relapse risk might be more effectively reduced with T cells expressing receptors (TCRs) that target selected AML antigens . We therefore isolated a high-affinity Wilms' Tumor Antigen 1-specific TCR (TCR ) from HLA-A2 normal donor repertoires, inserted TCR into Epstein-Bar virus-specific donor CD8 T cells (T ) to minimize graft-versus-host disease risk and enhance transferred T cell survival , 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). T maintained TCR expression, persisted long-term and were polyfunctional. This strategy appears promising for preventing AML recurrence in individuals at increased risk of post-HCT relapse.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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