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
Institution
Title
T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.
Journal
Nature medicine
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
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