HLA-A*24:02 presenting Wilms' tumor 1-derived peptide (HLA-A*24:02/WT1)

The HLA-A*24:02 presenting WT1-derived peptide is a peptide-major histocompatibility complex (pMHC) that serves as a specific target for cancer immunotherapy [1.1.1, 1.4.1]. It consists of a fragment of the Wilms' tumor 1 (WT1) protein, typically the 9-mer peptide CYTWNQMNL (WT1 235-243), bound to the HLA-A*24:02 molecule on the cell surface [1.2.1, 1.2.4]. WT1 is a transcription factor overexpressed in many cancers, including acute myeloid leukemia, myelodysplastic syndromes, and various solid tumors like pancreatic cancer and glioblastoma [1.2.1, 1.4.1]. Because WT1 is an intracellular protein, its presentation via HLA molecules is necessary for recognition by the cellular immune system [1.4.1]. This target is particularly significant in East Asian populations, where the HLA-A*24:02 allele is highly prevalent [1.1.1]. Therapeutic approaches include peptide vaccines like DSP-7888 and adoptive T-cell therapies (TCR-T) that utilize engineered T-cell receptors to recognize and kill cells displaying this complex [1.3.1, 1.4.3]. Clinical monitoring often involves assessing HLA-A*24:02 status and WT1 expression levels in tumor tissue [1.2.1, 1.3.2]. Safety considerations include potential off-target effects if the TCR cross-reacts with similar self-peptides and the risk of immune escape through HLA downregulation [1.4.1].

Other names

HLA-A*24:02/WT1(235-243)WT1-A24 complexHLA-A*24:02-restricted WT1 peptideCYTWNQMNL-HLA-A*24:02 complexWT1-235 peptide complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to cytotoxic T-lymphocyte (CTL) activation and lysis of WT1-expressing cells.