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SYNCAR-002 + STK-009 is an investigational combination therapy developed by Synthekine, utilizing their proprietary orthogonal IL-2 (orthoIL-2) technology. The regimen consists of two components: SYNCAR-002, an autologous chimeric antigen receptor T-cell (CAR-T) therapy targeting Glypican-3 (GPC3) that has been engineered to express a modified, orthogonal IL-2 receptor beta (hoRβ), and STK-009, an engineered, pegylated orthogonal IL-2 cytokine. STK-009 acts as a selective ligand ("key") that binds specifically to the engineered hoRβ receptor ("lock") on SYNCAR-002 cells, providing a private IL-2 proliferation and activation signal in vivo. This selective signaling is designed to enhance the expansion, persistence, and anti-tumor activity of the CAR-T cells within the tumor microenvironment while avoiding the systemic toxicities associated with wild-type IL-2 administration and potentially eliminating the need for lymphodepleting chemotherapy. The combination is currently in IND-enabling development for the treatment of hepatocellular carcinoma (HCC).
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