Wilms' tumor 1-derived peptide antigens presented by HLA class I (WT1-HLA-I complex)

Wilms' tumor 1 (WT1) is a zinc-finger transcription factor essential for urogenital development that is frequently overexpressed in a wide range of leukemias and solid tumors (Source: UniProt P19544). Within malignant cells, the WT1 protein undergoes proteasomal degradation into specific peptide fragments, which are then loaded onto Human Leukocyte Antigen (HLA) class I molecules and presented on the cell surface (Source: PubMed: 19622701). These peptide-HLA complexes act as specific targets for CD8+ cytotoxic T lymphocytes, allowing the immune system to identify and eliminate cancerous cells (Source: PubMed: 25710882). Due to the differential expression of WT1 between tumor and normal tissues, these complexes are highly attractive targets for cancer immunotherapy. 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-cells engineered with WT1-specific T-cell receptors (TCRs) (Source: Sellas Life Sciences; PubMed: 30635439). Additionally, TCR-like antibodies such as ESK1 are being developed to recognize these intracellular-derived antigens with the specificity of a T-cell and the potency of an antibody (Source: PubMed: 23486626).

Other names

WT1 peptide-MHC complexWT1-pMHCWilms tumor protein 1-derived antigensWT1-HLA complexWT1-HLA-A*02:01

Recognition of the peptide-HLA complex by specific T-cell receptors (TCRs) or TCR-like antibodies to induce targeted cell death of WT1-expressing malignant cells.