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

Details

Serval ID
serval:BIB_D60C7B1DD27D
Type
Article: article from journal or magazin.
Collection
Publications
Title
T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.
Journal
Nature medicine
Author(s)
Chapuis A.G., Egan D.N., Bar M., Schmitt T.M., McAfee M.S., Paulson K.G., Voillet V., Gottardo R., Ragnarsson G.B., Bleakley M., Yeung C.C., Muhlhauser P., Nguyen H.N., Kropp L.A., Castelli L., Wagener F., Hunter D., Lindberg M., Cohen K., Seese A., McElrath M.J., Duerkopp N., Gooley T.A., Greenberg P.D.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
07/2019
Peer-reviewed
Oui
Volume
25
Number
7
Pages
1064-1072
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 <sup>1-3</sup> . 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 <sup>4</sup> . 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 <sup>5</sup> . Thus, AML relapse risk might be more effectively reduced with T cells expressing receptors (TCRs) that target selected AML antigens <sup>6</sup> . We therefore isolated a high-affinity Wilms' Tumor Antigen 1-specific TCR (TCR <sub>C4</sub> ) from HLA-A2 <sup>+</sup> normal donor repertoires, inserted TCR <sub>C4</sub> into Epstein-Bar virus-specific donor CD8 <sup>+</sup> T cells (T <sub>TCR-C4</sub> ) to minimize graft-versus-host disease risk and enhance transferred T cell survival <sup>7,8</sup> , 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 <sub>TCR-C4</sub> maintained TCR <sub>C4</sub> expression, persisted long-term and were polyfunctional. This strategy appears promising for preventing AML recurrence in individuals at increased risk of post-HCT relapse.
Keywords
Adult, Aged, Female, Genes, T-Cell Receptor, Graft vs Host Disease/prevention & control, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Leukemia, Myeloid, Acute/mortality, Leukemia, Myeloid, Acute/therapy, Male, Middle Aged, Recurrence, Transplantation, Homologous, WT1 Proteins/genetics
Pubmed
Web of science
Create date
28/02/2022 11:45
Last modification date
23/03/2024 7:24
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