Wilms tumor protein 1-specific T-cell receptor (WT1-TCR) (WT1-TCR)

The Wilms tumor protein 1-specific T-cell receptor (WT1-TCR) is an engineered or naturally occurring immune receptor designed to recognize the Wilms tumor protein 1 (WT1) antigen. WT1 is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia (AML), and several solid tumors, including mesothelioma and ovarian cancer (PMID: 19723647). 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 (PMID: 30635445). In adoptive cell therapy, patient-derived T cells are genetically modified to express this TCR, enabling them to mount a targeted cytotoxic response against WT1-expressing malignant cells (PMID: 29305540). Clinical development of WT1-TCR therapies, such as JTCR016 and ASP7517, aims to provide a precision immunotherapy option for patients with refractory cancers (NCT02550535). However, therapeutic use is associated with risks such as cytokine release syndrome and potential on-target off-tumor toxicity due to low-level WT1 expression in normal tissues like the kidney and bone marrow (PMID: 31110039). The success of these therapies depends on the density of WT1 peptide-MHC complexes on the tumor surface and the persistence of the engineered T cells in the patient's circulation.

Other names

WT1-specific TCRWilms tumor 1-specific T-cell receptorWT1-targeted T-cell receptorWT1-TCR

Adoptive T-cell therapy (TCR-T) where engineered T cells express a TCR that recognizes WT1 peptide-MHC complexes, leading to targeted tumor cell lysis.