Wilms tumor protein 1 peptide-HLA-TCR interface (WT1-pHLA-TCR)

The Wilms tumor protein 1 (WT1) peptide-HLA-TCR interface is a tripartite molecular complex that serves as a critical target for cancer immunotherapy, particularly TCR-engineered T-cell therapies and multi-epitope vaccines. WT1 is a zinc-finger transcription factor that is highly overexpressed in a variety of hematological malignancies and solid tumors, while maintaining very low expression in healthy adult tissues (UniProt P19544). Because WT1 is an intracellular protein, it is processed by the proteasome into short peptides that are presented on the cell surface by Human Leukocyte Antigen (HLA) molecules. The interface is formed when a T-cell receptor (TCR) recognizes this peptide-HLA complex, leading to T-cell activation and the targeted destruction of the tumor cell (PubMed: 30333116). Drugs targeting this interface, such as the multi-epitope vaccine Galinpepimut-S, aim to stimulate the patient's own immune system to recognize these specific epitopes (ClinicalTrials.gov: NCT02520401). This target is particularly valuable because it allows the immune system to see intracellular oncogenic proteins that are otherwise invisible to antibody-based therapies. However, therapeutic success depends on the patient's HLA type and the avoidance of cross-reactivity with similar peptides in normal tissues.

Other names

WT1-MHC-TCR complexWilms tumor 1 antigen-HLA-TCR interfaceWT1 multi-epitope peptide-HLA-TCR complexWT1-pMHC-TCR interface

T-cell receptor binding to peptide-MHC complex and induction of cytotoxic T-lymphocyte response