Wilms Tumor 1-derived peptide–Major Histocompatibility Complex (WT1-pMHC) (WT1-pMHC)

Wilms Tumor 1-derived peptide–Major Histocompatibility Complex (WT1-pMHC) consists of short peptide fragments derived from the Wilms Tumor 1 (WT1) protein presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (Source: Nature Reviews Cancer). 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, including mesothelioma and ovarian cancer (Source: Journal of Hematology & Oncology). Because WT1 expression is minimal in healthy adult tissues, these pMHC complexes serve as highly specific targets for immunotherapy, allowing the immune system to recognize and eliminate cells expressing the intracellular WT1 protein (Source: Blood). Therapeutic strategies targeting WT1-pMHC include peptide vaccines like Galinpepimut-S, which aim to induce an endogenous T-cell response, and adoptive cell therapies using T-cells engineered with specific T-cell receptors (TCRs) (Source: SELLAS Life Sciences). Additionally, TCR-like monoclonal antibodies, such as ESK1, are designed to bind these complexes with high affinity and specificity (Source: Science Translational Medicine). Clinical application of these therapies often requires patients to possess specific HLA alleles, most commonly HLA-A*02:01 or HLA-A*24:02, to ensure proper peptide presentation and recognition (Source: Clinical Cancer Research).

Other names

WT1-HLA complexWilms tumor protein 1 peptide-MHCWT1-MHC class I complexWT1 peptide-HLA-A*02:01WT1 peptide-HLA-A*24:02

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) or TCR-mimetic antibodies to induce targeted lysis of tumor cells.