Wilms tumor 1–derived peptide–MHC class I complex (WT1-pMHC) (WT1-pMHC)

The Wilms tumor 1 (WT1)–derived peptide–MHC class I complex is a cell-surface molecular target formed when intracellular WT1 protein is processed by the proteasome and its resulting peptides are presented by Major Histocompatibility Complex (MHC) molecules (PMID: 19723653). WT1 is a zinc-finger transcription factor that is highly overexpressed in a wide range of hematological malignancies and solid tumors, while its expression in normal adult tissues is limited, making it an ideal tumor-associated antigen (UniProt P19544). Because WT1 is an intracellular protein, it is traditionally inaccessible to conventional monoclonal antibodies; however, the WT1-pMHC complex allows the immune system, specifically T-cell receptors (TCRs), to recognize and eliminate cancer cells (PMID: 23486626). Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies, TCR-mimic (TCRm) antibodies, and peptide vaccines designed to elicit a robust cytotoxic T-lymphocyte response (PMID: 26034288). Clinical development has focused on treating acute myeloid leukemia (AML) and various solid tumors, though challenges include strict HLA-restriction and potential off-target toxicity in tissues with low-level WT1 expression, such as the kidney (PMID: 30531451).

Other names

WT1-HLA complexWilms tumor protein 1 peptide-MHC complexWT1-MHC class I complexWT1-HLA-A*02:01 complexWT1 peptide-HLA complex

Targeting of the WT1-pMHC complex via engineered T-cell receptors (TCR-T) or TCR-mimic (TCRm) antibodies to induce direct T-cell mediated cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC) against tumor cells.