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

The Wilms' tumor 1 (WT1) peptide RMFPNAPYL presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. WT1 is a zinc-finger transcription factor that is overexpressed in many cancers, including acute myeloid leukemia (AML) and various solid tumors, making it a prominent tumor-associated antigen (PMID: 19196628). The RMFPNAPYL sequence (WT1 residues 126-134) is a highly immunogenic epitope that binds with high affinity to the HLA-A*02:01 allele, which is the most common MHC class I molecule in many human populations (PMID: 10833133). This complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then trigger the apoptosis of the target malignant cell. Therapeutic approaches targeting this pMHC include peptide vaccines like Galinpepimut-S, which aim to expand endogenous WT1-specific T cells, and adoptive cell therapies using TCR-engineered T cells (TCR-T) (PMID: 29343449). Additionally, TCR-mimetic antibodies and bispecific molecules are being developed to target this complex with antibody-like precision (PMID: 23486626). The primary challenge in targeting this pMHC is the potential for off-target toxicity if the therapeutic agent cross-reacts with similar peptides presented on healthy tissues (PMID: 31515463).

Other names

WT1(126-134) HLA-A*02:01RMFPNAPYL-HLA-A*02:01 complexWT1-A2 complexWilms tumor protein 1 epitope RMFPNAPYL

Targeting of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-mimetic antibodies to induce T-cell mediated lysis of tumor cells.