Wilms' tumor 1 peptide-HLA-A*24:02 complex (WT1/HLA-A*24:02)

The Wilms' tumor 1 (WT1) peptide-HLA-A*24:02 complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of various malignant cells. WT1 is a zinc-finger transcription factor that is highly overexpressed in many hematological malignancies and solid tumors, while remaining minimally expressed in normal adult tissues (Cheever et al., 2009, PMID: 19276362). Intracellular WT1 protein is degraded by the proteasome into short peptides, which are then loaded onto HLA-A*24:02 molecules for presentation on the cell surface. This specific complex is a critical target for cancer immunotherapies, particularly in populations where the HLA-A*24:02 allele is prevalent, such as in East Asia. Therapeutic strategies targeting this complex include peptide vaccines like DSP-7888 designed to stimulate endogenous cytotoxic T lymphocytes (CTLs) and adoptive cell therapies like TBI-1501 using engineered T-cell receptors (TCRs) (Sumitomo Pharma, 2021; Takara Bio, 2022). Successful binding by a TCR triggers a signaling cascade that leads to the directed release of perforins and granzymes, resulting in the apoptosis of the tumor cell. Clinical development has focused on indications such as acute myeloid leukemia (AML) and various solid cancers. Monitoring for HLA-A*24:02 positivity and WT1 expression levels is essential for patient selection in these therapies.

Other names

WT1-A24 complexHLA-A*24:02-restricted WT1 antigenWT1 peptide-MHC complexWT1-derived peptide-HLA-A*24:02

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and cytotoxic lysis of tumor cells (Oka et al., 2004, PMID: 15342353).