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

Wilms tumor protein 1 (WT1) is a zinc-finger transcription factor that plays a critical role in the development of the urogenital system and is highly overexpressed in various hematological malignancies and solid tumors (UniProt P19544). Because WT1 is an intracellular protein, it is not accessible to conventional antibodies; however, it is processed into short peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, primarily HLA-A*02:01 (PMID: 23486626). This WT1-MHC complex serves as a highly specific target for T-cell-based therapies, including TCR-engineered T cells and TCR-mimetic antibodies like ESK1 (PMID: 23486626). Therapeutic strategies, such as the peptide vaccine Galinpepimut-S, aim to exploit the differential expression of WT1 between malignant cells and normal tissues to induce targeted cell death (PMID: 30635445). While WT1 is a promising target, challenges include the requirement for specific HLA types in patients and potential low-level expression in normal tissues such as the kidney and bone marrow, which may lead to on-target off-tumor toxicities (PMID: 28655778).

Other names

WT1-HLA complexWilms tumor 1 antigenWT1 peptide-HLA-A*02:01WT1-MHC class I complexWT1-HLA-A2

Targeting of the WT1 peptide-MHC complex via T-cell receptors (TCRs), TCR-mimetic antibodies, or peptide vaccines to induce a cytotoxic immune response against WT1-expressing tumor cells.