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

The Wilms' tumor protein 1 (WT1) 126-134 epitope, specifically the RMFPNAPYL peptide, is a tumor-associated antigen presented by the Human Leukocyte Antigen (HLA)-A*02:01 molecule (Oka et al., 2000; PMID: 10833133). WT1 is a zinc-finger transcription factor that is essential for normal kidney and gonadal development but is highly overexpressed in various malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and several solid tumors (Cheever et al., 2009; PMID: 19276362). This peptide-MHC complex is a primary target for cancer immunotherapies, such as peptide vaccines (e.g., Galinpepimut-S) and T-cell receptor (TCR) engineered T-cell therapies, which aim to stimulate a cytotoxic T-lymphocyte (CTL) response against cells expressing the antigen (SELLAS Life Sciences, 2024; Di Stasi et al., 2015; PMID: 25352122). By specifically recognizing the RMFPNAPYL peptide in the context of HLA-A*02:01, these therapies facilitate the targeted destruction of tumor cells while sparing most healthy tissues. Clinical application requires patients to be HLA-A*02:01 positive and have tumors that express WT1. Potential therapeutic challenges include on-target, off-tumor toxicity in tissues with low WT1 expression and the potential for tumor immune evasion through HLA downregulation or antigen loss (Van Driessche et al., 2005; PMID: 15815701).

Other names

WT1 126-134RMFPNAPYL peptideWT1-A2 complexWilms' tumor protein 1 epitope RMFPNAPYLWT1 RMF peptide

Induction of a cytotoxic T-lymphocyte (CTL) response through the recognition of the RMFPNAPYL peptide presented by HLA-A*02:01 on the surface of tumor cells, leading to targeted cell lysis.