Wilms tumor 1 peptide–Major Histocompatibility Complex (WT1-MHC)

Wilms tumor 1 (WT1) is a zinc-finger transcription factor that plays a crucial role in cell growth and differentiation. While it is essential during embryonic development, its expression in adults is largely restricted to specific cells in the kidney, bone marrow, and mesothelium, but it is significantly upregulated in many cancers, including leukemia and various solid tumors (National Cancer Institute, 2009). Because WT1 is located within the nucleus, it cannot be targeted by standard antibody therapies. Instead, intracellular WT1 is processed into short peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02:01 or HLA-A*24:02 (PubMed: 23486629). This WT1 peptide–MHC complex serves as a highly specific target for T-cell receptor (TCR)-based therapies and TCR-like antibodies, which can recognize the peptide in the context of the MHC. Current clinical developments include TCR-engineered T cells, bispecific T-cell engagers, and peptide vaccines designed to trigger a cytotoxic immune response against WT1-presenting tumor cells (PubMed: 30104343).

Other names

WT1-HLA complexWilms tumor protein 1 peptide-HLA complexWT1 pMHCWT1 peptide-MHC class I complexWT1-specific pMHC

Targeting of the peptide-MHC complex via T-cell receptors (TCRs) or TCR-like antibodies to induce T-cell mediated lysis of tumor cells.