Details

Autor(en) / Beteiligte

• 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

Titel

T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant

Ist Teil von

• Nature medicine, 2019-07, Vol.25 (7), p.1064-1072

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.