Wilms' tumor 1 peptide–human leukocyte antigen complex (WT1-HLA complex) (WT1-HLA complex)

The Wilms' tumor 1 (WT1) peptide–human leukocyte antigen (HLA) complex is a primary target for T-cell-based cancer immunotherapies. WT1 is a zinc-finger transcription factor that is highly overexpressed in various leukemias and solid tumors, such as acute myeloid leukemia (AML) and ovarian cancer, but has restricted expression in normal adult tissues (Cheever et al., 2009, Clinical Cancer Research). The target consists of short WT1-derived peptides bound within the groove of HLA molecules on the tumor cell surface. These complexes are specifically recognized by the T cell receptors (TCRs) of CD8+ cytotoxic T cells or CD4+ helper T cells, which trigger T cell activation and subsequent tumor cell lysis (Sugiyama, 2010, Japanese Journal of Clinical Oncology). Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, which stimulate the patient's endogenous immune system, and adoptive TCR-T cell therapies that provide pre-engineered T cells to recognize the WT1-HLA complex (Maslak et al., 2018, Blood). Because the target is HLA-restricted, clinical application requires matching the therapeutic agent to the patient's specific HLA genotype, most commonly HLA-A*02:01 or HLA-A*24:02. Potential safety concerns include off-target effects on normal WT1-expressing cells, such as renal podocytes and hematopoietic stem cells (Ullrich et al., 2008, Blood). Monitoring WT1 expression levels and HLA status is essential for patient selection and assessing treatment efficacy.

Other names

WT1-MHC complexWT1-HLA-A*02:01WT1-HLA-A*24:02WT1-HLA-DRB1Wilms' tumor protein peptide-MHC complexWT1-pMHC

Induction of cytotoxic T lymphocyte (CTL) response and helper T cell response through specific recognition of WT1 peptides presented on HLA molecules, leading to the lysis of WT1-expressing tumor cells.