Human leukocyte antigen class I–Wilms' tumor 1 peptide complex (HLA-WT1)

The Human leukocyte antigen (HLA) class I–Wilms' tumor 1 (WT1) peptide complex is a cell-surface molecular assembly consisting of an HLA class I molecule and a short peptide fragment derived from the WT1 protein (UniProt P19544). WT1 is a transcription factor that is highly overexpressed in a wide range of hematological malignancies, such as acute myeloid leukemia, and various solid tumors, while maintaining restricted expression in normal adult tissues (National Cancer Institute, 2009). Because WT1 is an intracellular protein, it is inaccessible to conventional monoclonal antibodies; however, its degradation products are presented on the cell surface as peptide-MHC (pMHC) complexes, which can be recognized by CD8+ T cells (PubMed: 23486626). Therapeutic strategies targeting these complexes include peptide vaccines like Galinpepimut-S, which are designed to elicit endogenous T-cell responses, and TCR-engineered T-cell therapies (TCR-T) that provide high-affinity recognition of the complex (PubMed: 30104343). Additionally, TCR-mimic (TCRm) antibodies and bispecific molecules are being developed to bind the pMHC interface with high specificity (PubMed: 23486626). Clinical success depends on the precise selection of patients based on their HLA genotype and the level of WT1 expression in the tumor.

Other names

HLA-A*02:01/WT1 complexpMHC complex (WT1)WT1-peptide/HLA-A*02:01 complexWT1-HLA complexHLA-A*24:02/WT1 complex

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-mimic antibodies to induce T-cell mediated lysis of tumor cells.