Wilms' tumor protein 1-derived tumor-associated peptide antigens (WT1 peptides)

Wilms' tumor protein 1 (WT1)-derived tumor-associated peptide antigens are short peptide fragments derived from the intracellular WT1 protein, which are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (Sugiyama, 2010). WT1 is a zinc finger transcription factor that is highly overexpressed in a wide variety of hematological malignancies and solid tumors, including acute myeloid leukemia, myelodysplastic syndromes, and ovarian cancer (Oka et al., 2008). In contrast, its expression in normal adult tissues is restricted to specific sites like the kidney podocytes, gonads, and hematopoietic stem cells, making it a highly selective target (Nishida et al., 2022). These peptide-HLA complexes serve as critical targets for cancer immunotherapies, such as peptide vaccines, dendritic cell vaccines, and T-cell receptor (TCR)-engineered T-cell therapies (Oka et al., 2002). By targeting these antigens, the immune system can be trained to specifically recognize and destroy WT1-expressing malignant cells through the activation of cytotoxic T lymphocytes (CTLs) and helper T cells (Sugiyama, 2010). Due to its high immunogenicity and essential role in maintaining the oncogenic phenotype, WT1 has been ranked as the top priority cancer antigen for immunotherapy development (Cheever et al., 2009). Clinical trials have demonstrated that vaccines targeting these peptides, such as Galinpepimut-S, can induce robust immune responses and improve clinical outcomes in patients with minimal residual disease (SELLAS Life Sciences, 2024). However, the efficacy of these therapies is often limited by the patient's HLA type, as specific peptides only bind to certain HLA alleles like HLA-A*02:01 or HLA-A*24:02 (Oka et al., 2004).

Other names

WT1 epitopesWT1-derived peptidesWilms' tumor 1-derived peptidesWT1-derived CTL epitopesWT1-derived helper T-cell epitopesWT1-TAA

Induction of antigen-specific cytotoxic T lymphocytes (CTLs) and helper T cells that recognize and lyse WT1-expressing tumor cells via the T-cell receptor (TCR) interaction with peptide-MHC complexes.