Wilms' tumor 1-derived peptide–MHC class I complex (WT1-pMHC)

The Wilms' tumor 1 (WT1)-derived peptide–MHC class I complex is a molecular assembly presented on the cell surface that serves as a highly prioritized target for cancer immunotherapy (Cheever et al., 2009, Clinical Cancer Research). WT1 is a zinc-finger transcription factor that is overexpressed in a wide range of hematological malignancies, such as acute myeloid leukemia, and various solid tumors, while its expression in healthy adult tissues is restricted (Oka et al., 2004, Scientific Reports). Intracellular WT1 proteins are degraded into short peptide fragments, which are then loaded onto MHC class I molecules (most commonly HLA-A*02:01) and displayed on the plasma membrane. This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then initiate the destruction of the target cell. Current therapeutic approaches targeting this complex include peptide-based vaccines like Galinpepimut-S, TCR-engineered T-cell (TCR-T) therapies, and TCR-like antibodies that mimic the specificity of a T cell (Dao et al., 2013, Science Translational Medicine). Because the target is a peptide-MHC complex, clinical application is typically HLA-restricted, requiring patients to possess specific HLA alleles for the therapy to be effective (National Cancer Institute, 2023).

Other names

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

Recognition by T-cell receptors (TCRs) or TCR-mimetic antibodies to induce cytotoxic T-lymphocyte-mediated lysis of tumor cells.