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

The Wilms' tumor 1-specific T cell receptor (WT1-TCR) is an engineered or naturally derived receptor designed to recognize the WT1 protein, a transcription factor that is highly overexpressed in various leukemias and solid tumors but has limited expression in normal adult tissues [1]. This TCR specifically binds to WT1-derived peptides, such as the 126-134 or 235-243 sequences, when they are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, specifically the HLA-A*02:01 or HLA-A*24:02 alleles [2]. Upon recognition of the peptide-MHC complex, the TCR initiates a signaling cascade through the CD3 complex, leading to the activation of the T cell and the subsequent release of cytotoxic molecules like perforin and granzymes to destroy the target cancer cell [3]. WT1-TCR therapy is a prominent form of adoptive cell transfer (TCR-T) currently being evaluated in clinical trials for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) [4]. Because WT1 is ranked as a top priority cancer antigen by the National Cancer Institute, these TCRs represent a critical tool in precision oncology, though their use is restricted to patients carrying the appropriate HLA genotype [1][5].

Other names

WT1-targeted T cell receptorWT1/HLA-A*02:01-specific TCRWT1/HLA-A*24:02-specific TCRT cell receptor recognizing WT1-derived peptideWT1-specific TCR-T

TCR-engineered T cells (TCR-T) express this specific receptor to recognize WT1 peptides presented by HLA-A*02:01 or HLA-A*24:02 on tumor cells, triggering T cell activation, cytokine release, and direct tumor cell lysis [2][3].