Wilms' tumor 1-derived peptide epitopes presented by MHC class I (WT1-MHC I)

Wilms' tumor 1 (WT1) is a zinc-finger transcription factor essential for urogenital development, which is highly overexpressed in various leukemias and solid tumors while maintaining low expression in normal adult tissues [1, 2]. Intracellular WT1 is processed by the proteasome into short peptide epitopes, such as RMFPNAPYL or CMTWNQMNL, which are then presented on the cell surface by MHC class I molecules, typically HLA-A*02:01 or HLA-A*24:02 [3, 4]. These peptide-MHC complexes serve as specific targets for CD8+ cytotoxic T lymphocytes (CTLs), enabling the immune system to identify and eliminate malignant cells [2, 5]. Therapeutic strategies targeting these epitopes include peptide vaccines like Galinpepimut-S, which aim to prime the patient's own immune system, and adoptive T-cell therapies using TCR-engineered T cells (TCR-T) that provide a direct anti-tumor response [1, 6]. Because WT1 is an intracellular protein, the MHC-presented peptide is one of the few ways to target it using immunotherapy, though challenges include HLA downregulation by tumors and potential on-target, off-tumor effects in tissues like the kidney [4, 7]. This target is particularly significant in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), where WT1 expression is a known prognostic marker [1, 3].

Other names

WT1-HLA complexWT1 peptide-MHC complexWilms tumor 1 antigen epitopesWT1-derived MHC-I restricted peptidesWT1-pMHC

Therapeutic agents target the WT1-MHC I complex via T-cell receptors (TCRs) or TCR-like antibodies to induce a cytotoxic immune response against cells overexpressing the WT1 protein [3, 4].