Wilms' tumor 1 peptide-Human leukocyte antigen A*02 complex (WT1-HLA-A*02)

Wilms' tumor 1 (WT1) is an intracellular zinc-finger transcription factor that is highly overexpressed in a wide range of hematological malignancies and solid tumors, while showing very limited expression in normal adult tissues (NIH, 2014). Because WT1 is located within the cell, it cannot be targeted by traditional monoclonal antibodies; however, its degradation products are presented as peptides on the cell surface by Human Leukocyte Antigen (HLA) molecules (NIH, 2025). The peptide sequence RMFPNAPYL (residues 126-134) is a dominant immunogenic epitope that is specifically presented by the HLA-A*02:01 allele, making the WT1 peptide-HLA-A*02 complex a high-priority target for cancer immunotherapy (NIH, 2016). Therapeutic strategies targeting this complex include peptide vaccines designed to elicit endogenous T-cell responses, TCR-engineered T-cell therapies (TCR-T), and T-cell receptor-mimic (TCRm) antibodies or bispecifics that recognize the pMHC complex with high specificity (ResearchGate, 2024). Clinical applications focus on treating acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and various solid tumors like mesothelioma and ovarian cancer (MDPI, 2022). The complex is considered a validated target due to its tumor-specific presentation and the ability of specific T-cells to eliminate WT1-positive cells (BMJ, 2022).

Other names

WT1 peptide-HLA-A*02:01 complexWT1(126-134)/HLA-A*02:01 complexRMFPNAPYL/HLA-A*02:01 complexWT1-HLA-A2 complexWT1-MHC class I complexRMF/A2 complex

Drugs targeting this complex function by facilitating the recognition of the WT1 peptide-HLA-A*02 complex by the immune system. This is achieved through active immunization with WT1 peptides (vaccines) to induce endogenous cytotoxic T lymphocytes, the adoptive transfer of T-cells engineered with specific T-cell receptors (TCR-T), or the use of T-cell receptor-mimic (TCRm) antibodies and bispecific engagers that bind the complex and recruit effector cells to induce tumor cell lysis via apoptosis or antibody-dependent cellular cytotoxicity (ADCC).