Wilms tumor protein 1-derived peptide presented on Major Histocompatibility Complex (WT1-pMHC) (WT1-pMHC)

Wilms tumor protein 1 (WT1) is a zinc-finger transcription factor that serves as a critical regulator of gene expression during embryonic development and oncogenesis. While its expression is highly restricted in healthy adult tissues, it is significantly overexpressed in a wide range of hematological malignancies and solid tumors, making it a premier tumor-associated antigen. Because WT1 is an intracellular protein, it cannot be targeted by conventional monoclonal antibodies; instead, it is processed into short peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules. These peptide-MHC (pMHC) complexes, such as the RMFPNAPYL peptide presented by HLA-A*02:01, act as specific molecular signatures that can be recognized by T-cell receptors (TCRs). Therapeutic interventions targeting these complexes include peptide vaccines, TCR-engineered T cells (TCR-T), and TCR-mimetic bispecific antibodies, which aim to redirect the immune system to selectively destroy WT1-expressing malignant cells.

Other names

WT1 peptide-HLA complexWT1-MHC complexWilms tumor 1 peptide-MHC complexWT1-pMHC complexRMFPNAPYL-HLA-A*02:01 complex

Binding of therapeutic agents (TCRs or TCR-mimetic antibodies) to the specific peptide-MHC complex to trigger T-cell mediated cytotoxicity and apoptosis of the target tumor cell.