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

The Wilms' tumor 1 (WT1) peptide presented by HLA-A*02:01 is a highly prioritized tumor-associated antigen complex used in the development of targeted cancer immunotherapies. WT1 is a zinc-finger transcription factor that is overexpressed in a wide range of hematological malignancies, such as acute myeloid leukemia (AML), and solid tumors, including mesothelioma and ovarian cancer, while its expression in normal adult tissues is highly restricted (National Cancer Institute, 2023). Because WT1 is an intracellular protein, it cannot be targeted by traditional monoclonal antibodies; instead, it is processed into short peptides and presented on the cell surface by the HLA-A*02:01 molecule, the most common MHC class I allele in many populations (PubMed: 24610404). This peptide-MHC complex is specifically recognized by T-cell receptors (TCRs), enabling the use of TCR-engineered T-cell (TCR-T) therapies, peptide vaccines like Galinpepimut-S, and TCR-like bispecific antibodies (Nature Communications, 2020). These therapeutic approaches aim to induce a potent and specific cytotoxic T-cell response against cancer cells. However, clinical application requires careful monitoring for on-target, off-tumor toxicities in tissues with low-level WT1 expression, such as the kidneys and hematopoietic stem cells, as well as systemic inflammatory responses like cytokine release syndrome (Journal of Hematology & Oncology, 2021).

Other names

WT1-A2 complexHLA-A*02:01/WT1(126-134)WT1 peptide-MHC complexWilms' tumor protein peptide-HLA-A*02:01RMFPNAPYL-HLA-A*02:01

T-cell mediated cytotoxicity via recognition of the peptide-MHC complex by engineered or endogenous T-cell receptors (TCRs) or TCR-like molecules.