Wilms tumor protein 1-derived peptide presented on HLA molecules (WT1-HLA complex)

The Wilms tumor protein 1 (WT1)-derived peptide presented on HLA molecules is a critical target in cancer immunotherapy, representing a complex formed by intracellularly processed WT1 fragments and Human Leukocyte Antigen (HLA) class I molecules. WT1 is a zinc-finger transcription factor that plays a pivotal role in cell growth and differentiation, and it is highly overexpressed in a wide range of hematological malignancies and solid tumors, including acute myeloid leukemia (AML) and mesothelioma (Cheever et al., 2009; Oka et al., 2004). Because WT1 is an intracellular protein, it is not accessible to traditional antibody therapies; however, its degradation into peptides and subsequent presentation on the cell surface via HLA molecules allows for recognition by T-cells. Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, which stimulate the patient's own immune system, and adoptive T-cell therapies using T-cell receptors (TCRs) engineered to recognize the specific WT1-HLA complex (Maslak et al., 2018). The specificity of this target is largely determined by the particular HLA allele, such as HLA-A*02:01, making patient HLA typing a prerequisite for treatment. While highly promising, challenges include potential on-target off-tumor toxicity in tissues with low WT1 expression, such as the kidneys and bone marrow, and the risk of immune evasion through HLA downregulation (Di Stasi et al., 2015).

Other names

WT1-MHC complexWT1 peptide-HLA-A*02:01Wilms tumor 1 antigen complexWT1-HLA-A2 complex

T-cell receptor (TCR) binding and activation of cytotoxic T-lymphocytes (CTLs) to induce apoptosis in WT1-expressing cells