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

The Wilms tumor 1 (WT1) peptide-Major Histocompatibility Complex (MHC) class I complex is a prominent target for cancer immunotherapy due to the high overexpression of the WT1 transcription factor in hematological malignancies like acute myeloid leukemia (AML) and various solid tumors (Source: UniProt P19544; PubMed: 23486660). WT1 is processed intracellularly into peptides, such as the RMFPNAPYL decamer, which are presented on the cell surface by MHC class I molecules, most commonly HLA-A*02:01 (Source: PubMed: 23486660). This complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making it a focal point for TCR-engineered T-cell (TCR-T) therapies and bispecific antibodies (Source: ClinicalTrials.gov NCT04580134). Therapeutic agents like Galinpepimut-S act as vaccines to stimulate endogenous T-cell responses against this complex, while bispecifics like RG6007 (RO7284755) facilitate direct T-cell engagement (Source: Sellas Life Sciences; Roche Pipeline). Because WT1 is also expressed at low levels in normal tissues such as the renal podocytes and mesothelium, safety monitoring for on-target off-tumor toxicity is essential (Source: PubMed: 11759411). Effective targeting requires patient screening for both WT1 expression and specific HLA genotypes to ensure the presence of the correct pMHC complex (Source: PubMed: 28630100).

Other names

WT1-HLA complexWT1-MHC complexHLA-A*02:01/WT1 peptide complexWilms tumor protein 1-MHC class I complexWT1-pMHC

Redirection of T-cell cytotoxicity through TCR-mediated recognition of the WT1 peptide-MHC complex.