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

The T-cell receptor on Wilms' tumor 1-specific T lymphocytes (WT1-TCR) is a specialized protein complex used in adoptive cellular immunotherapy to target malignancies expressing the Wilms' tumor 1 (WT1) antigen (National Cancer Institute, 2023). WT1 is a zinc-finger transcription factor that is highly overexpressed in various leukemias and solid tumors while maintaining limited expression in normal adult tissues, making it an attractive target for cancer therapy (UniProt P19544). The WT1-TCR recognizes specific WT1-derived peptides, such as RMFPNAPYL, presented by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01 (Chapuis et al., Nature Medicine, 2019). When these engineered T cells encounter WT1-presenting tumor cells, the TCR triggers T-cell activation, leading to the release of cytotoxic granules and cytokines that destroy the target cell. Clinical development of WT1-TCR-T therapies focuses primarily on acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) (ClinicalTrials.gov NCT02770820). However, therapeutic challenges include potential on-target off-tumor toxicity in tissues with low-level WT1 expression, such as the renal podocytes, and the risk of cytokine release syndrome (Tawara et al., 2017). Additionally, the efficacy of these therapies is often limited by the requirement for specific HLA matching and the potential for tumor escape through HLA downregulation.

Other names

WT1-specific T-cell receptorWilms' tumor 1-targeted TCRWT1-TCRT-cell receptor on WT1-specific T cells

Engineered T-cell receptors recognize specific WT1 peptide fragments presented by HLA molecules on the surface of tumor cells, initiating a signaling cascade that results in T-cell proliferation and cytotoxic destruction of the cancer cell (Chapuis et al., 2019).