Wilms tumor 1-derived peptide epitopes presented by HLA-A*02:01 MHC class I (WT1/HLA-A*02:01)

The Wilms tumor 1 (WT1) protein is a zinc-finger transcription factor that plays a critical role in cell growth and differentiation (UniProt P19544). While its expression is limited in healthy adult tissues, it is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia (AML), and several solid tumors, making it an attractive target for immunotherapy (PubMed 10717038). The WT1-derived peptide epitopes, specifically those presented by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule, serve as specific markers for T-cell recognition (PubMed 28408464). Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, T-cell receptor (TCR) engineered T-cell therapies, and TCR-like antibodies or bispecific molecules (ClinicalTrials.gov NCT02527109). These therapies aim to harness the immune system to selectively eliminate WT1-positive malignant cells while sparing normal tissues. However, potential on-target off-tumor effects on the kidney or bone marrow must be monitored due to low-level WT1 expression in those tissues (PubMed 22517177). The HLA-A*02:01 restriction is particularly significant as it is one of the most prevalent HLA alleles in the global population, facilitating broad clinical application.

Other names

WT1-A2 complexWT1 peptide-HLA-A*02:01WT1 RMFPNAPYL/HLA-A*02:01WT1 126-134 peptideWT1 187-195 peptideWT1 pMHC complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation and cytotoxic destruction of the target cell.