Wilms' tumor 1 (37-45) peptide presented by HLA-A*02:01 (WT1 37-45/HLA-A*02:01)

The WT1 37-45 peptide presented by HLA-A*02:01 is a specific tumor-associated antigen complex consisting of a 9-amino acid fragment (VLDFAPPGA) derived from the Wilms' tumor 1 (WT1) protein, bound to the human leukocyte antigen (HLA) allele A*02:01 (1.2.3, 1.3.1). WT1 is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), as well as several solid tumors, including glioblastoma and ovarian cancer (1.1.1, 1.1.2). While WT1 is essential for urogenital development, its expression in healthy adult tissues is limited, leading the National Cancer Institute to rank it as a top priority target for cancer immunotherapy (1.2.3, 1.1.4). The 37-45 epitope is particularly significant because it is processed and presented independently of the immunoproteasome, allowing it to remain visible to the immune system even when tumor cells downregulate immunoproteasome subunits to evade other WT1-targeted therapies like the 126-134 epitope (1.2.4). Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies, peptide-based vaccines such as adegramotide, and TCR-mimic antibodies, all of which aim to induce T-cell mediated destruction of WT1-positive malignant cells (1.4.2, 1.4.4).

Other names

WT1 37-45VLDFAPPGA peptideWT1-37VLD/A2Wilms tumor protein 37-45pWT1 37-45

T-cell mediated cytotoxicity via TCR recognition of the peptide-MHC complex