Wilms' tumor 1 peptide-Human leukocyte antigen class I complex (WT1-HLA-I) (WT1-HLA-I)

The Wilms' tumor 1 (WT1) peptide–Human leukocyte antigen (HLA) class I complex is a cell-surface molecular target formed by the presentation of intracellularly processed WT1 protein fragments on HLA class I molecules. WT1 is a zinc-finger transcription factor that is highly overexpressed in a wide range of hematological malignancies, such as acute myeloid leukemia, and various solid tumors, while maintaining very low expression in normal adult tissues (Cheever et al., 2009, Clinical Cancer Research). This differential expression makes the WT1-HLA complex an ideal target for precision immunotherapy. Because WT1 is an intracellular protein, it cannot be targeted by traditional monoclonal antibodies; instead, it must be recognized as a peptide fragment presented by the Major Histocompatibility Complex (MHC) (Dao et al., 2013, Science Translational Medicine). Current therapeutic approaches include T-cell receptor (TCR) gene-modified T cells, TCR-mimic antibodies like ESK1, and peptide vaccines such as Galinpepimut-S designed to elicit a cytotoxic T-lymphocyte response against cells displaying these complexes (Oren et al., 2014, Blood).

Other names

WT1-MHC class I complexWT1-HLA complexWT1-pMHCWilms' tumor 1-HLA-A*02:01 complex

Targeted recognition of the WT1 peptide-HLA complex by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies, leading to the activation of cytotoxic immune responses against tumor cells.