Human leukocyte antigen A*02:01 presenting Wilms tumor protein 1 126-134 epitope (HLA-A*02:01/WT1(126-134))

The HLA-A*02:01-restricted Wilms tumor protein 1 (WT1) 126-134 epitope is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy (Oka et al., 2004, PubMed: 14710016). The Wilms tumor protein 1 (WT1) is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia (AML), and several solid tumors, while maintaining limited expression in normal adult tissues (Keilholz et al., 2009, PubMed: 19664484). The specific nonameric peptide sequence RMFPNAPYL (residues 126-134) is processed intracellularly and presented on the cell surface by the HLA-A*02:01 allele, which is the most common MHC Class I molecule in Caucasian populations (Sugiyama, 2010, PubMed: 20624191). Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, TCR-engineered T cells (TCR-T), and TCR-like bispecific antibodies, which are designed to recognize the pMHC with high specificity (Dao et al., 2013, PubMed: 23486779). These therapies aim to leverage the specificity of the T-cell receptor to selectively eliminate malignant cells presenting the WT1 antigen. However, therapeutic development faces challenges such as potential on-target off-tumor toxicity due to low-level WT1 expression in the kidneys and hematopoietic stem cells (Rosenfeld et al., 2003, PubMed: 12663359).

Other names

WT1 126-134 peptide-HLA-A*02:01 complexRMFPNAPYL-HLA-A*02:01WT1-A2 complexWilms tumor protein 1 epitope 126-134HLA-A*02:01-restricted WT1 epitope

Binding of therapeutic T-cell receptors (TCRs) or TCR-like antibodies to the peptide-MHC complex, triggering cytotoxic immune responses against the target cell.