Wilms' tumor protein peptide–MHC complex (WT1-pMHC)

The Wilms' tumor protein (WT1) peptide–MHC complex is a specialized therapeutic target representing the cell-surface presentation of the intracellular WT1 transcription factor. WT1 is a zinc-finger protein that plays a vital role in urogenital development but is pathologically overexpressed in various hematological malignancies, such as acute myeloid leukemia (AML), and solid tumors like ovarian cancer and mesothelioma (Cheever et al., 2009; Sugiyama, 2001). Since WT1 is an intracellular protein, it cannot be targeted by traditional monoclonal antibodies; instead, it is processed by the proteasome into short peptides that are displayed on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (Dao et al., 2013). This presentation allows the immune system to identify and eliminate malignant cells through T-cell recognition. Current therapeutic approaches targeting this complex include peptide vaccines like Galinpepimut-S, which stimulate the patient's own immune response, and adoptive cell therapies such as TCR-engineered T-cells that are programmed to bind specifically to the WT1-pMHC complex (Di Stasi et al., 2011; SELLAS Life Sciences, 2024).

Other names

WT1-HLA complexWilms' tumor 1-MHC complexWT1 peptide-HLA-A*02:01 complexWT1 peptide-HLA-A*24:02 complexWT1-pMHC

Recognition and binding by T-cell receptors (TCRs) or TCR-mimetic antibodies, triggering cytotoxic T-lymphocyte mediated destruction of the target cell.