Wilms tumor protein 1-derived peptides presented on Major Histocompatibility Complex (WT1-MHC complex)

Wilms tumor protein 1 (WT1) is a zinc-finger transcription factor that plays a critical role in cell growth and differentiation (UniProt P19544). While its expression is limited in healthy adult tissues to specific sites like the kidneys and hematopoietic stem cells, it is highly overexpressed in a wide range of hematological malignancies and solid tumors, earning it a top ranking as a priority cancer antigen by the National Cancer Institute (Cheever et al., 2009, Clinical Cancer Research). Intracellular WT1 proteins are degraded by the proteasome into short peptides, which are then transported to the cell surface and presented by Major Histocompatibility Complex (MHC) molecules, specifically Human Leukocyte Antigens (HLA) such as HLA-A*02:01 (PubMed: 10833477). This WT1-MHC complex serves as a crucial target for various immunotherapeutic strategies, including peptide vaccines like Galinpepimut-S, T-cell receptor (TCR) gene-modified T-cells, and TCR-like antibodies (PubMed: 30104343). These therapies aim to exploit the differential expression of WT1 to selectively eliminate cancer cells while sparing most normal tissues, though potential on-target, off-tumor effects on WT1-expressing healthy cells remain a therapeutic challenge (PubMed: 28454154).

Other names

WT1 peptide-HLA complexWilms tumor 1 antigenWT1-derived epitopesWT1 peptide-MHCWT1-HLA-A*02:01 complex

Recognition of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies to trigger cytotoxic T-lymphocyte-mediated lysis of tumor cells (PubMed: 30104343).