Wilms' tumor 1 antigen presented on MHC class I (WT1-pMHC)

Wilms' tumor 1 (WT1) is a zinc-finger transcription factor that plays a dual role as an oncogene and a tumor suppressor, depending on the cellular context. It is essential for the normal development of the urogenital system, but its overexpression is a hallmark of many hematological malignancies, such as acute myeloid leukemia (AML), and various solid tumors. Because WT1 is an intracellular protein, it is not accessible to conventional monoclonal antibodies; however, it is processed into peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules. This peptide-MHC (pMHC) complex serves as a highly specific target for T-cell-based immunotherapies, including peptide vaccines, T-cell receptor (TCR)-engineered T cells, and TCR-mimic antibodies. These therapeutic approaches aim to activate or redirect the patient's immune system to recognize and eliminate WT1-expressing cancer cells. Clinical development of WT1-targeted therapies often requires patient selection based on both WT1 expression levels and specific Human Leukocyte Antigen (HLA) types, such as HLA-A*02:01 or HLA-A*24:02.

Other names

WT1 peptide-MHC complexWT1/HLA complexWilms' tumor 1 peptide-HLA complexRMF/A2 complexWT1-HLA-A*02:01WT1-HLA-A*24:02

T-cell activation, T-cell redirection, immune stimulation, and antibody-dependent cellular cytotoxicity (ADCC) via recognition of intracellularly derived peptides presented on the cell surface by MHC class I molecules.