Wilms' tumor 1 peptide-MHC class I complex (WT1-pMHC)

The Wilms' tumor 1 (WT1) peptide-MHC class I complex is a tumor-associated antigen consisting of a processed fragment of the WT1 transcription factor bound to a Major Histocompatibility Complex (MHC) molecule. WT1 is pathologically overexpressed in a wide range of hematological malignancies and solid tumors, while its expression in healthy adult tissues is highly restricted (Cheever et al., 2009). Because WT1 is an intracellular protein, it is traditionally undruggable by standard monoclonal antibodies; however, its degradation products are presented on the cell surface as peptides (such as RMFPNAPYL) via MHC class I molecules (Oka et al., 2004). This peptide-MHC complex serves as a specific molecular signature that allows the immune system to identify and eliminate malignant cells. Therapeutic strategies targeting this complex include peptide vaccines like Galinpepimut-S, which stimulate endogenous T-cell responses, and adoptive cell therapies using TCR-engineered T cells (TCR-T) or TCR-like antibodies (Dao et al., 2013). The target is highly prioritized in oncology due to its broad expression across different cancer types and its essential role in maintaining the oncogenic phenotype.

Other names

WT1 peptide-HLA complexWilms' tumor protein-derived peptide presented on MHC class IWT1-HLA-A*02:01 complexWT1-HLA-A*24:02 complexRMFPNAPYL-HLA-A*02:01

Therapeutic agents target the WT1-pMHC complex through T-cell receptor (TCR) binding or TCR-like antibody recognition to trigger the lysis of WT1-expressing tumor cells by cytotoxic T lymphocytes.