Wilms' tumor 1-derived RMFPNAPYL peptide presented by HLA-A*02:01 (WT1(126-134)/HLA-A*02:01)

The Wilms' tumor 1 (WT1)-derived RMFPNAPYL peptide presented by HLA-A*02:01 is a specific peptide-MHC (pMHC) complex that serves as a critical target for cancer immunotherapy. WT1 is a zinc-finger transcription factor essential for urogenital development but is pathologically overexpressed in many cancers, including acute myeloid leukemia (AML) and various solid tumors (1, 2). The RMFPNAPYL sequence, representing residues 126-134 of the WT1 protein, is a dominant immunogenic epitope that is processed and presented by the HLA-A*02:01 allele (3). This complex acts as a molecular flag on the surface of cancer cells, allowing the immune system to distinguish malignant cells from most healthy tissues. Therapeutic interventions targeting this pMHC complex include peptide-based vaccines, such as Galinpepimut-S, which aim to prime the patient's endogenous T cells (4). Additionally, advanced modalities like TCR-engineered T-cell (TCR-T) therapies and TCR-mimetic bispecific antibodies are being developed to provide a direct, potent attack against cells displaying this specific antigen (5). Clinical utility is restricted to patients who are HLA-A*02:01 positive and whose tumors demonstrate significant WT1 expression. (1) UniProtKB - P19544; (2) PubMed: 10833143; (3) PubMed: 22547534; (4) NCI Drug Dictionary; (5) ClinicalTrials.gov.

Other names

WT1 RMF peptideWT1 126-134 peptideHLA-A*02:01/WT1(126-134) complexRMFPNAPYL-HLA-A*02:01WT1-A2 complex

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) or TCR-mimetic antibodies to trigger cytotoxic T-lymphocyte mediated apoptosis of the target cell.