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

The Wilms tumor 1 (WT1) peptide–Human leukocyte antigen (HLA) class I complex is a cell-surface molecular target formed by the presentation of intracellularly processed WT1 protein fragments on HLA molecules. WT1 is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies and solid tumors, while its expression in normal adult tissues is limited (Oka et al., 2004, PubMed: 15150584). As an intracellular protein, WT1 cannot be targeted by standard antibodies; however, its presentation as a peptide-MHC complex allows for recognition by T-cell-based immunotherapies. This complex is specifically targeted by TCR-engineered T-cells (TCR-T), TCR-like antibodies (e.g., ESK1), and bispecific T-cell engagers (e.g., RG6007) (Dao et al., 2013, Science Translational Medicine). These therapies aim to induce a potent and selective immune response against WT1-positive malignant cells. Clinical focus is often on the HLA-A*02:01 restricted peptide RMFPNAPYL, which is one of the most immunogenic WT1 epitopes (Sugiyama, 2010, Japanese Journal of Clinical Oncology). Despite its promise, safety concerns include potential "on-target, off-tumor" effects in tissues like the kidney or bone marrow where low levels of WT1 are present.

Other names

WT1-MHC class I complexWT1 pMHCWilms tumor 1 antigen-HLA complexWT1-HLA-A*02:01 complex

Therapeutic agents such as TCR-engineered T-cells or TCR-like antibodies bind specifically to the WT1 peptide presented within the HLA class I groove. This binding event triggers an immune-mediated attack, typically via the release of perforins and granzymes from cytotoxic T lymphocytes, leading to the selective apoptosis of the WT1-expressing tumor cells.