HLA-A*02:01-Wilms' tumor 1 (37-45) peptide complex (HLA-A2/WT1-37 complex)

The HLA-A2–WT1-37 peptide complex is a specific peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*02:01 molecule and the VLDFAPPGA peptide, which is derived from the 37-45 amino acid sequence of the Wilms' tumor 1 (WT1) protein. 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 very low expression in healthy adult tissues. The WT1-37 epitope is particularly significant because its processing and presentation are independent of the immunoproteasome, allowing it to remain visible to the immune system even in tumor cells that have downregulated immunoproteasome subunits to escape other T-cell responses. This complex serves as a critical target for advanced immunotherapies, including TCR-engineered T cells (TCR-T) and TCR-mimic antibodies, which are designed to specifically recognize and eliminate cells presenting this intracellularly derived antigen. Clinical and preclinical studies have demonstrated that targeting the HLA-A2/WT1-37 complex can circumvent resistance mechanisms associated with more common WT1 epitopes like WT1-126, making it a promising candidate for treating relapsed or refractory cancers.

Other names

HLA-A*02:01/WT1(37-45)WT1-37/HLA-A2 complexVLDFAPPGA-HLA-A2 complexWT1 37-45 peptide-MHC complexHLA-A2-restricted WT1-37 epitope

Recognition of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-mimic antibodies, which triggers cytotoxic T-lymphocyte (CTL) mediated apoptosis of the target tumor cell.