Targeting an alternate Wilms' tumor antigen 1 peptide bypasses immunoproteasome dependency.

ABSTRACT: Designing effective antileukemic immunotherapy will require understanding mechanisms underlying tumor control or resistance. Here, we report a mechanism of escape from immunologic targeting in an acute myeloid leukemia (AML) patient, who relapsed 1 year after immunotherapy with engineered T cells expressing a human leukocyte antigen A*02 (HLA-A2)-restricted T cell receptor (TCR) specific for a Wilms' tumor antigen 1 epitope, WT1_126-134 (T_TCR-C4). Resistance occurred despite persistence of functional therapeutic T cells and continuous expression of WT1 and HLA-A2 by the patient's AML cells. Analysis of the recurrent AML revealed expression of the standard proteasome, but limited expression of the immunoproteasome, specifically the beta subunit 1i (β1i), which is requir

SUBMITTER: Lahman MC 

PROVIDER: S-EPMC8985599 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature