Acute Myeloid Leukemia Skews Therapeutic WT1-specific CD8 TCR-T Cells Towards an NK-like Phenotype that Compromises Function and Persistence.

ABSTRACT: Acute myeloid leukemia (AML) that is relapsed and/or refractory post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. In a prior study, we demonstrated that AML relapse in high-risk patients was prevented by post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8⁺ T cells engineered to express a high-affinity Wilms Tumor Antigen 1 (WT1)-specific T-cell receptor (T_TCR-C4). However, in the present study, infusion of EBV- or Cytomegalovirus (CMV)-specific T_TCR-C4 did not clearly improve outcomes in fifteen patients with active disease post-HCT. TCR_C4-transduced EBV-specific T cells persisted longer post-transfer than CMV-specific T cells. Persisting T_TCR-C4 skewed towards dysfunctional natural killer-l

SUBMITTER: Mazziotta F 

PROVIDER: S-EPMC11702715 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature