Wilms' tumor 1 peptide–Major histocompatibility complex class I complex (WT1-MHC I) (WT1-MHC I)

The Wilms' tumor 1 (WT1) peptide–Major histocompatibility complex (MHC) class I complex is a cell-surface molecular assembly consisting of a processed WT1-derived peptide bound within the groove of an MHC class I molecule. WT1 is a zinc-finger transcription factor that plays a crucial role in cell growth and differentiation, and its overexpression is linked to the pathogenesis of numerous hematological malignancies and solid tumors (Source: Cheever et al., Clin Cancer Res, 2009). As an intracellular protein, WT1 is inaccessible to standard antibody therapies; however, its presentation as a peptide-MHC complex on the cell surface enables targeting by the cellular immune system. Modern therapeutic approaches, including TCR-engineered T cells (TCR-T), bispecific T-cell engagers, and TCR-like monoclonal antibodies, are designed to specifically recognize this complex to trigger tumor cell lysis (Source: Dao et al., Sci Transl Med, 2013). This target is particularly valuable in oncology due to the high tumor-to-normal tissue expression ratio of WT1, providing a therapeutic window for precision immunotherapy.

Other names

WT1-HLA complexWT1-pMHCWilms' tumor 1 peptide-HLA-A*02:01 complexWT1-HLA-A2 complexWilms' tumor protein peptide-MHC complex

Targeting of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-like antibodies to induce T-cell mediated cytotoxicity against cells expressing the WT1 antigen.