Wilms tumor 1 peptide–Major Histocompatibility Complex (WT1-MHC) (WT1-MHC)

The Wilms tumor 1 (WT1) peptide–Major Histocompatibility Complex (MHC) is a tumor-associated antigen complex that presents intracellularly derived peptides on the surface of malignant cells. WT1 is a zinc-finger transcription factor that plays a vital role in urogenital development but is pathologically overexpressed in a variety of hematological malignancies, such as acute myeloid leukemia (AML), and solid tumors like ovarian and lung cancer (Source: PubMed, PMID: 17401011). Because WT1 is an intracellular protein, it is not accessible to conventional antibody therapies; however, its degradation into peptides and subsequent presentation by MHC Class I molecules (typically HLA-A*02:01) creates a unique surface target (Source: UniProt, P19544). This complex is recognized by the T-cell receptor (TCR), making it a primary focus for TCR-engineered T-cell therapies and TCR-like monoclonal antibodies (Source: PubMed, PMID: 23486629). Drugs targeting this complex, such as the vaccine Galinpepimut-S or TCR-based cell therapies, aim to stimulate or provide a direct cytotoxic immune response against cancer cells while leveraging the high differential expression of WT1 between malignant and healthy tissues.

Other names

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

Recognition of the intracellularly derived WT1 peptide presented on the cell surface by MHC molecules, leading to T-cell receptor (TCR) mediated activation and subsequent lysis of the target cell.