Wilms tumor protein peptide-HLA class I complex (WT1-HLA complex)

The Wilms tumor protein (WT1) peptide-HLA class I complex is a highly validated target for cancer immunotherapy, particularly in hematological malignancies and various solid tumors [1, 3]. WT1 is an intracellular zinc-finger transcription factor that plays a dual role as a tumor suppressor in pediatric Wilms tumors and an oncogene in many adult cancers, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) [1, 20]. Although WT1 is located within the nucleus, it is processed by the proteasome into short peptides that are presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, such as HLA-A*02:01 and HLA-A*24:02 [2, 16]. These peptide-HLA complexes serve as specific markers for immune recognition, enabling the development of therapies like peptide vaccines (e.g., Galinpepimut-S), TCR-engineered T cells, and TCR-mimic antibodies (e.g., ESK1) [2, 12, 14]. By targeting these complexes, therapies aim to achieve high specificity for malignant cells while sparing normal tissues, which express WT1 at significantly lower levels [1, 18]. However, clinical challenges include potential off-target effects on WT1-expressing normal tissues like the kidney and bone marrow, as well as the risk of immune escape through antigen loss [4, 9, 11].

Other names

WT1/HLA complexWT1 peptide-MHC complexWilms tumor 1 peptide-HLA complexWT1-derived HLA class I epitopesWT1-MHC class I complex

Induction of cytotoxic T lymphocyte (CTL) response, antibody-dependent cellular cytotoxicity (ADCC), and T-cell receptor (TCR) mediated cell killing.