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

The Wilms' tumor 1 (WT1) peptide–Major Histocompatibility Complex (pMHC) is a critical immunological target in oncology, particularly for hematological malignancies and solid tumors (Nature Reviews Cancer, 2009). WT1 is a zinc-finger transcription factor that is highly overexpressed in cancers like acute myeloid leukemia (AML) but has limited expression in normal adult tissues (UniProt P19544). On the surface of dendritic cells or tumor cells, processed WT1 peptides are presented by MHC molecules, such as HLA-A*02:01, to be recognized by specific T-cell receptors (TCRs) (Journal of Hematology & Oncology, 2018). This interaction is the basis for therapeutic strategies including peptide vaccines like Galinpepimut-S and TCR-engineered T-cell (TCR-T) therapies (SELLAS Life Sciences; PMID: 29301555). Binding of the TCR to the WT1-pMHC complex triggers T-cell activation and the subsequent cytotoxic destruction of malignant cells. The specificity of this interaction is vital for minimizing off-target effects, although potential toxicity in WT1-expressing healthy tissues remains a concern.

Other names

WT1-HLA complexWT1 antigen-MHC complexWilms tumor protein 1 peptide-MHCWT1-MHC class I complex

Induction of antigen-specific T-cell response through TCR recognition of the peptide-MHC complex, leading to cytotoxic T-lymphocyte activation and tumor cell lysis.