Wilms' tumor 1 protein RMFPNAPYL peptide–HLA-A*02:01 complex (WT1 RMF-HLA-A*02:01) (WT1 RMF-HLA-A*02:01)

The Wilms' tumor 1 (WT1) protein RMFPNAPYL peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy (Cheever et al., 2009, Clinical Cancer Research). The RMFPNAPYL sequence, representing amino acids 126–134 of the WT1 protein, is an immunodominant epitope presented by the HLA-A*02:01 allele, which is prevalent in many populations (Oka et al., 2004, Cancer Research). WT1 is a transcription factor overexpressed in various malignancies, including acute myeloid leukemia (AML) and several solid tumors, while its expression in healthy tissues is highly restricted. This complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering a targeted immune response against tumor cells. Therapeutic approaches targeting this complex include TCR-engineered T-cell therapies (e.g., JTCR016), TCR-like monoclonal antibodies (e.g., ESK1), and peptide vaccines like Galinpepimut-S (Dao et al., 2013, Science Translational Medicine; SELLAS Life Sciences, 2024). Clinical development focuses on leveraging this specificity to treat WT1-positive cancers while monitoring for potential 'on-target, off-tumor' toxicities in tissues like the kidney or bone marrow where WT1 is expressed at low levels.

Other names

WT1(126-134) HLA-A*02:01 complexRMFPNAPYL-HLA-A*02:01WT1-A2 complexWT1 peptide-MHC complexWT1 pMHC

Recognition by engineered or endogenous T-cell receptors (TCRs) or TCR-like antibodies, leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of cells presenting the WT1 peptide.