Wilms' tumor 1-derived peptide VLDFAPPGA in complex with HLA-A*01:01 (WT1-VLD/HLA-A*01:01)

The Wilms' tumor 1 (WT1)-derived peptide VLD/A1 refers to the specific peptide-major histocompatibility complex (pMHC) consisting of the VLDFAPPGA peptide (WT1 residues 37-45) presented by the Human Leukocyte Antigen (HLA)-A*01:01 molecule. WT1 is a zinc-finger transcription factor that is overexpressed in a variety of hematological malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), as well as solid tumors like ovarian cancer and mesothelioma. Because WT1 expression is very low in most normal adult tissues, the VLD/A1 complex serves as a highly specific tumor-associated antigen for immunotherapy. Current therapeutic strategies targeting this complex include the multi-peptide vaccine Galinpepimut-S and engineered T-cell receptor (TCR-T) therapies, which aim to activate or provide T-cells that specifically recognize and kill cells displaying this pMHC. A primary safety concern in targeting WT1 is the potential for on-target, off-tumor toxicity, particularly in the kidneys where WT1 is expressed in podocytes. Clinical development requires screening patients for both WT1 overexpression and the HLA-A*01:01 genotype to ensure target presence and treatment efficacy.

Other names

WT1-VLD/A1WT1 peptide 37-45/HLA-A*01:01VLDFAPPGA-HLA-A*01:01 complexWT1-VLDWT1-A01

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