Wilms' tumor protein 1 (WT1) peptide-HLA-A*02:01 complex (WT1-HLA-A*02:01)

The Wilms' tumor protein 1 (WT1) peptide-HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of tumor cells (Oka et al., 2004). WT1 is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies and solid tumors, while maintaining very low expression in normal adult tissues, making it a top-ranked cancer antigen (Cheever et al., 2009). The HLA-A*02:01 allele is the most prevalent MHC class I molecule in many populations, facilitating the presentation of the WT1-derived nonamer peptide, such as RMFPNAPYL, to CD8+ T cells (Lichtenegger et al., 2023). Therapeutic strategies targeting this complex include TCR-engineered T cells (TCR-T), bispecific T-cell engagers, and peptide vaccines like Galinpepimut-S designed to elicit a robust cytotoxic T-lymphocyte response (Sellamuthu et al., 2022). Because the target is an intracellular protein processed and presented via the MHC pathway, it allows for the targeting of oncogenic drivers that are otherwise inaccessible to traditional monoclonal antibodies. Clinical development focuses on ensuring high specificity to avoid cross-reactivity with similar peptides in healthy tissues to prevent off-target toxicity.

Other names

WT1-A2 complexHLA-A*02:01-restricted WT1 epitopeRMFPNAPYL-HLA-A*02:01 complexWT1 peptide-MHC class I complexWilms' tumor 1 antigen

The complex serves as a specific ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, triggering a signaling cascade that leads to the directed release of cytotoxic granules and the lysis of the WT1-expressing tumor cell (Oka et al., 2004; Lichtenegger et al., 2023).