Wilms' tumor 1-derived peptide epitopes presented on human leukocyte antigen (WT1-HLA complex)

Wilms' tumor 1 (WT1) is a zinc-finger transcription factor that is essential for the development of the urogenital system but is highly overexpressed in a wide variety of hematological and solid malignancies (Source: UniProt P19544). The National Cancer Institute has previously ranked WT1 as the top priority cancer antigen due to its high expression in tumors, immunogenicity, and oncogenic function (Source: Cheever et al., Clin Cancer Res 2009). Because WT1 is an intracellular protein, it is not accessible to traditional monoclonal antibodies; instead, it is processed by the proteasome into short peptide fragments and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules. These WT1-HLA complexes serve as the specific target for T-cell-based immunotherapies, including peptide vaccines like Galinpepimut-S and TCR-engineered T-cell (TCR-T) therapies (Source: SELLAS Life Sciences). The clinical application of these therapies is typically restricted to patients carrying specific HLA alleles, most commonly HLA-A*02:01 or HLA-A*24:02, which are required to present the WT1 peptides to the immune system. Therapeutic development focuses on maximizing T-cell recognition of these pMHC complexes while minimizing off-target effects on normal tissues that express low levels of WT1, such as the kidneys and bone marrow (Source: PubMed PMID: 30633422).

Other names

WT1-pMHC complexWilms' tumor 1 peptide-MHCWT1-HLA-A*02:01WT1-HLA-A*24:02WT1-derived neoantigenWT1-HLA-A2

Targeting of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-mimetic antibodies to induce T-cell mediated cytotoxicity and lysis of tumor cells expressing the WT1 antigen.