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

The Wilms' tumor 1 (WT1) peptide-HLA class I complex is a tumor-associated antigen formed when the intracellular WT1 transcription factor is processed into peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules. WT1 is highly overexpressed in various hematological malignancies and solid tumors, such as acute myeloid leukemia and mesothelioma, while maintaining very low expression in normal adult tissues (Source: PubMed: 25691326). Because WT1 is an intracellular protein, it cannot be targeted by standard monoclonal antibodies; however, the presentation of its peptides via HLA allows the immune system to recognize and eliminate malignant cells. Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, which stimulate endogenous T-cell responses, and adoptive cell transfers using T-cell receptor (TCR)-engineered T-cells (Source: SELLAS Life Sciences, PubMed: 30531450). These therapies are typically HLA-restricted, most commonly targeting the HLA-A*02:01 allele, requiring patient screening for both WT1 expression and specific HLA types.

Other names

WT1-MHC complexWT1-HLA-A*02:01 complexWilms' tumor protein peptide-HLA complexWT1-pMHC

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