Wilms tumor protein 1 peptide-HLA-A*02:01 complex (WT1/HLA-A*02:01)

The Wilms tumor protein 1 (WT1) peptide-HLA-A*02:01 complex is a tumor-associated antigen consisting of a processed WT1 peptide fragment presented by the Human Leukocyte Antigen (HLA) class I molecule A*02:01 (ImmunoScape, 2024). WT1 is a transcription factor essential for urogenital development that is frequently overexpressed in a wide range of cancers, including acute myeloid leukemia (AML) and various solid tumors, while maintaining low expression in healthy tissues (National Cancer Institute). This differential expression makes the WT1/HLA-A*02:01 complex a high-priority target for T-cell receptor (TCR) based immunotherapies (ImmunoScape, 2024). Therapeutic candidates like IS-001 employ TCR-engineered T cells designed to bind specifically to this pMHC complex, triggering a cytotoxic immune response against malignant cells (ImmunoScape, 2024). The efficacy of targeting this complex can be further enhanced by co-administration of agents like CUE-102, which act as selective T-cell engagers to expand the population of WT1-specific T cells in the patient's body (Cue Biopharma, 2024). Clinical development focusing on this target aims to provide a precision medicine approach for patients who are HLA-A*02:01 positive and have WT1-expressing tumors (Sellas Life Sciences, 2024). Safety considerations for this target include potential off-target cross-reactivity with similar peptides and on-target off-tumor effects in tissues like the kidney where WT1 is physiologically expressed (ImmunoScape, 2024).

Other names

WT1-A2 complexWT1 RMFPNAPYL/HLA-A*02:01Wilms tumor 1 antigenWT1 peptide-MHC complexWT1(126-134)/HLA-A*02:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and targeted lysis of tumor cells.