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

The Wilms' tumor protein 1 (WT1) peptide-HLA class I complex is a tumor-associated antigen complex presented on the surface of malignant cells. WT1 is a transcription factor that is highly overexpressed in various hematological malignancies and solid tumors, while its expression in normal adult tissues is limited to low levels in the kidney, bone marrow, and mesothelial cells (UniProt P19544). Because WT1 is an intracellular protein, it cannot be targeted by traditional antibodies; however, its degradation into peptides and subsequent presentation by Human Leukocyte Antigen (HLA) class I molecules allows it to be recognized by the immune system (PubMed: 17409438). Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies (TCR-T), TCR-mimetic bispecific antibodies, and peptide vaccines like Galinpepimut-S (PubMed: 28603122). These therapies aim to leverage the specificity of the TCR-peptide-HLA interaction to selectively eliminate cancer cells while sparing healthy tissue. However, potential on-target, off-tumor toxicity remains a concern due to low-level WT1 expression in vital organs like the kidney and bone marrow (PubMed: 22535994).

Other names

WT1-MHC complexWT1 peptide-MHC class I complexWT1-HLA-A*02:01 complexWilms' tumor 1 antigen complexWT1-pMHC

T-cell receptor (TCR) engagement and subsequent T-cell mediated lysis of target cells