Wilms tumor protein 1-derived peptide epitopes presented by Human Leukocyte Antigen A*02 (WT1/HLA-A*02)

Wilms tumor protein 1 (WT1) is a zinc-finger transcription factor that plays a critical role in cell proliferation, differentiation, and apoptosis (UniProt P19544). While its expression is limited in healthy adult tissues, it is highly overexpressed in various hematological malignancies and solid tumors, leading the National Cancer Institute to rank it as a top priority cancer antigen (Cheever et al., 2009). The target specifically refers to WT1-derived peptides, such as the immunodominant RMFPNAPYL sequence, which are processed and presented on the cell surface by the Human Leukocyte Antigen A*02 (HLA-A2) molecule (Oka et al., 2004). This peptide-MHC complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T-lymphocytes, triggering an anti-tumor immune response. Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, designed to elicit endogenous immune responses, as well as adoptive T-cell therapies (e.g., JTCR016) and bispecific antibodies (e.g., RG6007) (Maslak et al., 2018; Roche). Clinical development focuses on patients who are HLA-A*02 positive and have WT1-expressing tumors, particularly in the context of acute myeloid leukemia and myelodysplastic syndromes.

Other names

WT1-HLA-A2 complexWT1 peptide-MHC complexWilms tumor 1 peptide-HLA-A*02:01 complexWT1-A2

Recognition of the specific peptide-MHC complex by T-cell receptors (TCRs) or TCR-like antibodies, leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of tumor cells.