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The WT1-specific T cell receptor is an α/β heterodimeric immunoreceptor expressed on the surface of CD8+ T cells—either naturally or via genetic engineering—designed to recognize WT1 peptide epitopes presented by MHC class I molecules on malignant cells. WT1, a transcription factor aberrantly expressed in many cancers, serves as a tumor-associated antigen. WT1-specific TCRs can be used to redirect patient or donor CD8+ T cells to selectively kill WT1-expressing cancer cells, and form the basis for innovative immunotherapies such as peptide vaccines and adoptive TCR-T cell therapies. Clinical and preclinical studies have demonstrated potent antitumor activity and specificity, although safety monitoring is critical due to possible on-target toxicity and immunological challenges.
Recognition of WT1 peptide/MHC complexes on malignant cells. Initiation of cytotoxic T lymphocyte (CTL) activity, resulting in target cell lysis/apoptosis. Cytokine production (e.g., IFN-γ) upon antigen recognition. Memory T cell formation for durable immune response. Engineered TCR-T cell therapy uses gene transfer to endow patient T cells with high-affinity WT1-specific TCRs.
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