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

The Wilms tumor 1 (WT1) protein is a zinc-finger transcription factor that plays a vital role in the development of the urogenital system and is frequently overexpressed in various cancers (Source: NIH). The target 'WT1-derived peptide presented by HLA class I' refers to the complex formed when WT1 protein is processed into short peptides and displayed on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, such as HLA-A*02:01 (Source: UniProt). This peptide-MHC (pMHC) complex is a critical target for cancer immunotherapy because it allows the immune system to identify intracellular proteins that are otherwise inaccessible to standard antibodies (Source: PubMed). Therapeutic interventions targeting this complex include TCR-engineered T-cell therapies (TCR-T), TCR-like monoclonal antibodies, and peptide vaccines like Galinpepimut-S, which aim to induce a cytotoxic T-lymphocyte response against tumor cells (Source: ClinicalTrials.gov). While WT1 is a highly validated tumor-associated antigen, therapeutic challenges include potential 'on-target, off-tumor' toxicity in healthy tissues that express low levels of WT1, such as renal podocytes and hematopoietic stem cells (Source: PubMed). Additionally, tumors may escape immune detection by downregulating HLA expression or through other mechanisms of immune evasion (Source: Nature Reviews Cancer).

Other names

WT1-pMHC complexWT1 peptide-HLA complexWilms tumor protein 1 peptide-MHCWT1-HLA-A*02:01 complex

Recognition of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-like molecules to trigger cytotoxic immune responses and lysis of WT1-expressing cells.