Wilms' tumor protein 1-derived peptide-HLA complex (WT1-pHLA)

Wilms' tumor protein 1 (WT1) is a zinc-finger transcription factor that plays a critical role in the development of the urogenital system but is highly overexpressed in various hematological malignancies and solid tumors (Oka et al., 2004; PubMed: 15034312). The target consists of specific WT1-derived peptide fragments presented on the cell surface by Human Leukocyte Antigen (HLA) Class I or Class II molecules. These peptide-HLA (pHLA) complexes serve as specific markers for immune recognition, allowing the immune system to distinguish malignant cells from healthy ones (Dao et al., 2013; Science Translational Medicine). Therapeutic strategies targeting these complexes include peptide vaccines designed to elicit an endogenous immune response, TCR-engineered T-cell (TCR-T) therapies, and TCR-like antibodies or bispecific molecules that mimic T-cell receptor specificity (Sumitomo Pharma; SELLAS Life Sciences). Because WT1 is often considered a "universal" tumor antigen due to its broad expression across different cancer types and limited expression in normal adult tissues, it is a high-priority target for cancer immunotherapy. However, potential safety concerns include on-target off-tumor effects in tissues with low-level WT1 expression, such as the renal podocytes and hematopoietic stem cells.

Other names

WT1 peptide-MHC complexWT1-HLA complexWilms' tumor 1 antigenWT1-derived peptide epitopes bound to HLA class I/IIWT1-MHC

T-cell receptor (TCR) or TCR-like antibody recognition of WT1 peptide-HLA complexes, leading to targeted lysis of tumor cells via cytotoxic T-lymphocyte activation or antibody-mediated effector functions.