Wilms tumor protein 1-derived peptide-MHC complex (WT1-pMHC)

The Wilms tumor protein 1 (WT1)-derived peptide-MHC complex is a prominent target in oncology, facilitating the immune recognition of an otherwise inaccessible intracellular transcription factor. WT1 is highly expressed in a variety of hematological and solid malignancies, including acute myeloid leukemia (AML) and mesothelioma, while maintaining minimal expression in healthy tissues such as the kidney and bone marrow (Source: PMID: 19723653). Intracellular WT1 is processed by the proteasome into short peptides, which are then transported to the cell surface and presented by Major Histocompatibility Complex (MHC) class I molecules, most commonly HLA-A*02:01 or HLA-A*24:02 (Source: PMID: 26034288). This presentation allows the complex to be targeted by T-cell receptor (TCR)-based therapies, including peptide vaccines like Galinpepimut-S and TCR-engineered T-cells (TCR-T), which are designed to selectively kill cells displaying the WT1-pMHC signature (Source: PMID: 30635439). Because the target is defined by both the peptide and the specific MHC allele, patient selection requires screening for both WT1 expression and the appropriate HLA haplotype to ensure therapeutic efficacy (Source: PMID: 28246111).

Other names

WT1 peptide-HLA complexWilms tumor 1 peptide-MHCWT1-MHC class I complexWT1-HLA-A*02:01 complexWilms tumor protein 1-derived peptide-HLA complex

The target is recognized by T-cell receptors (TCRs) or TCR-like antibodies that specifically bind to the interface formed by the WT1-derived peptide and the MHC/HLA groove. This interaction triggers the activation of cytotoxic T-lymphocytes (CTLs), leading to the release of perforins and granzymes that induce apoptosis in the target tumor cell (Source: PMID: 28246111, PMID: 30635439).