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

The Wilms' tumor 1-specific T-cell receptor (WT1-TCR) is a synthetic or affinity-enhanced receptor introduced into a patient's T cells to treat cancers overexpressing the WT1 protein (Sugiyama, 2010). WT1 is a transcription factor that plays a crucial role in cell growth and differentiation, and its overexpression is a hallmark of many leukemias and solid tumors, making it a high-priority target for immunotherapy (Rampal et al., 2021). The engineered TCR is specifically designed to bind to WT1 peptide fragments, such as the RMFPNAPYL sequence, when presented by specific human leukocyte antigen (HLA) alleles like HLA-A*02:01 (Nature Communications, 2020). Once the TCR-T cell identifies its target on a tumor cell, it initiates a potent cytotoxic response involving the secretion of granzymes and cytokines like interferon-gamma (Journal of Hematology & Oncology, 2021). This mechanism allows for the precise elimination of cancer cells that might otherwise evade the natural immune system. Current clinical applications primarily target acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), where WT1 expression is particularly high (Takara Bio, 2023). However, challenges remain regarding the persistence of these cells in the body and the potential for on-target, off-tumor toxicity in tissues with low-level WT1 expression, such as the kidneys or bone marrow (PubMed, 2022).

Other names

WT1-specific TCRWilms' tumor protein 1-specific T-cell receptorWT1-targeted T-cell receptorWT1-TCR

Engineered T-cell receptors recognize specific Wilms' tumor 1 (WT1) peptide fragments presented by human leukocyte antigen (HLA) molecules on the surface of tumor cells, triggering T-cell activation, cytokine release, and direct cytotoxic lysis of the target cell.