Wilms' tumor 1-specific T-cell receptor (WT1-TCR)

The Wilms' tumor 1-specific T-cell receptor (WT1-TCR) is an engineered or naturally occurring immune receptor designed to recognize the Wilms' tumor 1 (WT1) antigen, a prominent tumor-associated protein (Cheever et al., 2009, PubMed: 19723909). WT1 is a transcription factor that is highly overexpressed in various cancers, including acute myeloid leukemia (AML) and several solid tumors, while showing limited expression in healthy adult tissues (Tawara et al., 2017, PubMed: 28115365). The WT1-TCR specifically identifies WT1-derived peptides presented by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 or HLA-A*24:02 (Lichtenegger et al., 2020, PubMed: 32071159). Upon recognition of the peptide-MHC complex, the TCR triggers a signaling cascade within the CD8+ T cell, leading to the release of cytotoxic molecules like granzymes and perforins, as well as pro-inflammatory cytokines (June et al., 2018, PubMed: 29880682). This interaction results in the selective destruction of WT1-expressing malignant cells. As a key component of TCR-T cell therapy, the WT1-TCR allows the immune system to target intracellular oncogenic proteins that are not accessible to conventional antibody-based treatments (Schuster et al., 2018, PubMed: 30124778).

Other names

WT1-specific T-cell receptorWT1-directed T-cell receptorT-cell receptor targeting Wilms' tumor 1

Engineered WT1-specific TCRs bind to WT1 peptide-HLA complexes on the surface of tumor cells, initiating T-cell receptor signaling, which induces T-cell proliferation, cytokine production, and direct cytotoxic killing of the target cell (June et al., 2018, PubMed: 29880682).