DKN-01 + tislelizumab

DKN-01 + tislelizumab is an investigational combination therapy comprised of two monoclonal antibodies: DKN-01, which targets and neutralizes Dickkopf-related protein 1 (DKK1), and tislelizumab, an anti–programmed cell death protein 1 (PD-1) antibody. DKN-01 acts by blocking DKK1, a modulator of Wnt signaling associated with tumor angiogenesis, proliferation, and immunosuppression. Blocking DKK1 leads to enhanced innate immune response and downregulation of cancer cell survival pathways. Tislelizumab is designed to inhibit the PD-1/PD-L1 immune checkpoint pathway, allowing for improved anti-tumor immune activity, and is Fc-optimized to minimize antibody-dependent phagocytosis by macrophages. This combination has been investigated in clinical trials for advanced gastric or gastroesophageal junction adenocarcinoma, with or without chemotherapy (CAPOX or mFOLFOX6), showing encouraging activity and manageable toxicity, especially in patients with elevated DKK1 expression or low PD-L1 levels[1][2][3][4][5][6][7][9][10].