Wilms' tumor 1 peptide–Major Histocompatibility Complex (WT1-MHC) (WT1-MHC)

The Wilms' tumor 1 (WT1) peptide–Major Histocompatibility Complex (MHC) is a tumor-associated antigen complex formed when the intracellular WT1 protein is processed into peptides and presented on the cell surface by MHC Class I molecules (Source: PubMed, PMID: 17401010). WT1 is a transcription factor that plays a vital role in urogenital development but is pathologically overexpressed in numerous cancers, including acute myeloid leukemia, mesothelioma, and various solid tumors (Source: UniProt, P19544). As an intracellular target, WT1 cannot be reached by standard antibodies; however, the peptide-MHC complex allows the immune system to detect internal cellular abnormalities (Source: National Cancer Institute). Therapeutic strategies targeting this complex include TCR-engineered T cells (TCR-T), TCR-like antibodies, and peptide vaccines designed to trigger a cytotoxic T-cell response against malignant cells (Source: PubMed, PMID: 23486660). While highly promising due to the high differential expression between tumor and normal tissues, therapeutic development must account for the HLA-restriction of the peptides and potential off-tumor toxicity in normal WT1-expressing tissues like the kidney and bone marrow (Source: PubMed, PMID: 21220455).

Other names

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

Targeting of the peptide-MHC complex by T-cell receptors or TCR-like antibodies to induce T-cell mediated cytotoxicity against tumor cells.