Wilms' tumor 1 peptide–HLA-A*01 complex (WT1-HLA-A*01)

The Wilms' tumor 1 (WT1) peptide–HLA-A*01 complex is a specific antigen-presenting structure found on the surface of cells, particularly malignant ones (Cheever et al., 2009, Clinical Cancer Research). WT1 is a transcription factor that is highly overexpressed in various leukemias and solid tumors, while having limited expression in normal adult tissues, making it an ideal tumor-associated antigen (Oka et al., 2004, Journal of Immunology). When WT1 protein is degraded intracellularly, its peptides are loaded onto Human Leukocyte Antigen (HLA) molecules, such as the HLA-A*01 allele, and transported to the cell surface (Oka et al., 2004, Journal of Immunology). This complex is then recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune response against the target cell (Cheever et al., 2009, Clinical Cancer Research). Therapeutic interventions targeting this complex include peptide vaccines like Galinpepimut-S, which aim to expand endogenous WT1-specific T cells (SELLAS Life Sciences, 2024). Other approaches involve adoptive cell therapies using TCR-engineered T cells or bispecific T-cell engagers designed to bind the pMHC with high affinity. These therapies are primarily investigated for the treatment of acute myeloid leukemia (AML) and other WT1-positive malignancies in patients carrying the HLA-A*01 allele. Monitoring WT1 expression levels and HLA-A*01 status is crucial for patient selection and assessing therapeutic efficacy.

Other names

WT1-A01 complexWT1-HLA-A*01:01 complexWilms tumor protein peptide-MHC complexWT1 pMHC

Induction of T-cell mediated cytotoxicity through recognition of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-mimetic molecules.