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

Wilms' tumor 1 (WT1) is a zinc-finger transcription factor essential for normal urogenital development but is frequently overexpressed in a wide range of hematological malignancies and solid tumors (National Cancer Institute, 2009). MHC class I–presented WT1 peptides are short fragments of the WT1 protein that are processed intracellularly and displayed on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, specifically Human Leukocyte Antigens (HLA) (PubMed, PMID: 28630100). These peptide-MHC complexes serve as highly specific targets for the immune system, allowing CD8+ cytotoxic T cells to identify and eliminate malignant cells. Because WT1 expression is significantly higher in cancer cells compared to most healthy adult tissues, these complexes are prime targets for immunotherapies (UniProt, P19544). Current therapeutic approaches include peptide-based vaccines like Galinpepimut-S designed to stimulate endogenous T-cell responses, as well as adoptive cell therapies using T-cell receptors (TCRs) or bispecific T-cell engagers engineered to recognize the WT1-pMHC complex (ClinicalTrials.gov, NCT04251013).

Other names

WT1 peptide-HLA complexMHC-presented WT1 peptidesWT1-MHC complexHLA-restricted WT1 antigen

Therapeutic agents target the specific peptide-MHC complex to trigger T-cell mediated cytotoxicity against cells overexpressing the WT1 protein. This is achieved through vaccines that induce endogenous T-cell expansion or through engineered TCR-T cells and bispecific antibodies that provide direct recognition of the WT1-pMHC complex (Nature Reviews Cancer, 2021).