Wilms Tumor 1-specific T cell receptor (WT1 TCR) (WT1 TCR)

The T cell receptor (TCR) on IS-001 engineered T cells is a synthetic, high-affinity receptor designed to target the Wilms Tumor 1 (WT1) antigen. WT1 is a well-validated oncofetal protein and transcription factor that is overexpressed in a wide range of hematological and solid malignancies, such as ovarian cancer, mesothelioma, and acute myeloid leukemia, but has limited expression in healthy adult tissues (immunoscape.com). The IS-001 therapy, developed by ImmunoScape, utilizes these engineered T cells in a "Seed and Boost" clinical strategy (academicjobs.com). In this regimen, the TCR-T cells are first infused into the patient, followed by the administration of CUE-102, a WT1-specific IL-2-based fusion protein that selectively binds to the engineered TCR to promote the expansion and persistence of the therapeutic T cells in vivo (immunoscape.com). This dual approach is intended to overcome the common challenges of T cell exhaustion and poor persistence in the immunosuppressive tumor microenvironment. By targeting the intracellular WT1 antigen through the TCR, the therapy can address solid tumors that are typically inaccessible to conventional antibody-based treatments.

Other names

IS-001 TCRWT1-specific T cell receptorT cell receptor on IS-001 engineered T cells

The TCR specifically recognizes the Wilms Tumor 1 (WT1) peptide presented by HLA-A*02:01 on tumor cells, triggering T cell activation and cytotoxic killing. Additionally, it is selectively expanded in vivo through binding with the CUE-102 fusion protein.