Wilms' tumor 1 peptide-Major Histocompatibility Complex class I complex (WT1-pMHC I)

The Wilms' tumor 1 (WT1) peptide-Major Histocompatibility Complex (MHC) class I complex is a specialized therapeutic target used in cancer immunotherapy. WT1 is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia, and several solid tumors, while maintaining very low expression in healthy adult tissues (Cheever et al., 2009, Clinical Cancer Research). 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 MHC class I molecules (Dao et al., 2013, Science Translational Medicine). This pMHC complex is recognized by the T-cell receptor (TCR) of CD8+ T cells, triggering an immune response against the cancer cell. Modern therapeutic approaches, including TCR-engineered T cells (TCR-T) and TCR-mimetic bispecific antibodies, are designed to specifically bind this complex to eliminate WT1-positive malignant cells (NCT02773303). This target is particularly valuable because it allows the immune system to recognize intracellular oncogenic drivers that are otherwise hidden from surface-level surveillance.

Other names

WT1-HLA complexWT1 peptide-MHC complexWT1-pMHCWilms' tumor 1 antigen-MHC class IWT1-HLA-A*02:01

Engagement of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies to facilitate T-cell mediated cytotoxicity against tumor cells.