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

The Wilms' tumor 1 (WT1) peptide–HLA class I complex is a tumor-associated antigen presented on the surface of malignant cells. WT1 is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia, and several solid tumors, while maintaining low expression in normal tissues (Cheever et al., 2009; PMID: 19276362). Because WT1 is an intracellular protein, it is not accessible by traditional monoclonal antibodies; however, its degradation products are processed and presented by Human Leukocyte Antigen (HLA) molecules, most commonly HLA-A*02:01, for recognition by the immune system (Dao et al., 2013; PMID: 23486626). This peptide-MHC (pMHC) complex serves as a specific target for advanced immunotherapies, including T-cell receptor (TCR) engineered T-cells and TCR-mimic (TCRm) antibodies. These therapies are designed to bind the complex with high specificity, triggering a cytotoxic immune response against the cancer cell while sparing healthy tissue (Ochoa et al., 2020; PMID: 32661115). Clinical development of agents targeting this complex is a major focus in oncology, particularly for patients with WT1-positive and HLA-matched malignancies.

Other names

WT1-HLA-A*02:01 complexWT1-MHC complexWT1-derived peptide–MHC class I complexWT1-pMHC complexWilms' tumor 1 antigen–HLA complex

Targeting of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-mimic antibodies to induce T-cell mediated lysis of tumor cells.