Wilms' tumor 1 protein (WT1) (WT1)

Wilms' tumor 1 protein (WT1) is a zinc-finger transcription factor that plays a dual role as both a tumor suppressor and an oncogene, depending on the cellular context and the specific isoforms expressed (UniProt: P19544). While essential for the normal development of the urogenital system, WT1 is highly overexpressed in a variety of hematological malignancies and solid tumors, where it promotes cell survival, proliferation, and resistance to apoptosis (PMID: 28407455). Because WT1 is an intracellular protein, it cannot be targeted by conventional monoclonal antibodies; however, its degradation products are presented as peptide epitopes on the cell surface via MHC class I molecules. This presentation makes WT1 a high-priority target for T-cell-based immunotherapies, including peptide vaccines, TCR-engineered T cells, and TCR-mimetic antibodies (NCI: Cheever et al., 2009). Current clinical strategies focus on inducing or providing high-affinity T-cell receptors that recognize these specific WT1-MHC complexes to selectively eliminate malignant cells while minimizing impact on healthy tissues.

Other names

Wilms tumor proteinWT33GUDWAGRWIT-2Amino-terminal proline-rich domain zinc finger protein

Induction of a cytotoxic T-lymphocyte (CTL) response or direct T-cell engagement targeting specific WT1-derived peptide epitopes (e.g., RMFPNAPYL) presented by Major Histocompatibility Complex (MHC) class I molecules on the surface of tumor cells (PMID: 19723663, 31515463).