Wilms' tumor 1-derived peptide – HLA class I complex (WT1-HLA-I)

The Wilms' tumor 1 (WT1)-derived peptide – HLA class I complex is a tumor-associated antigen complex presented on the surface of malignant cells. WT1 is a zinc-finger transcription factor that plays a crucial role in cell growth and differentiation; while its expression is low in healthy adult tissues, it is highly overexpressed in various leukemias and solid tumors (National Cancer Institute, 2023). Intracellular WT1 protein is degraded by the proteasome into short peptides, which are then transported into the endoplasmic reticulum and loaded onto Human Leukocyte Antigen (HLA) class I molecules for presentation to CD8+ T cells (PubMed: 28334915). This specific peptide-MHC presentation makes the intracellular WT1 protein visible to the immune system from the outside. Therapeutic interventions targeting these complexes include peptide vaccines designed to elicit an endogenous immune response, and adoptive T-cell therapies using T-cell receptors (TCRs) engineered to recognize the WT1-HLA complex with high affinity (Nature Reviews Cancer, 2021). Additionally, TCR-like bispecific antibodies are being developed to bridge T cells to cells presenting these specific complexes, facilitating targeted tumor cell lysis (Blood, 2020). The success of these therapies is highly dependent on the patient's HLA haplotype and the density of the complex on the tumor cell surface.

Other names

WT1 peptide-MHC complexWT1-pMHCWT1-HLA-A*02:01 complexWilms tumor protein 1 peptide-HLA complexWT1-derived peptide-MHC class I complex

Drugs targeting this complex function by specifically binding to the peptide-HLA interface, mimicking the natural recognition by T-cell receptors (TCRs) to trigger an immune-mediated attack against the tumor cell (Nature Reviews Drug Discovery, 2022). This interaction leads to the activation of cytotoxic T lymphocytes (CTLs) or the recruitment of effector cells via bispecific molecules, resulting in the selective lysis of cells presenting the WT1-derived peptide (Blood, 2020).