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This combination therapy is being investigated as a first-line treatment for advanced hepatocellular carcinoma (HCC). It consists of three distinct agents: **H101 (Oncorine)**, an oncolytic virus; **tislelizumab**, a monoclonal antibody; and **lenvatinib**, a small molecule kinase inhibitor. H101 is a recombinant human adenovirus type 5 engineered with a deletion of the E1B-55kDa gene, which allows it to selectively replicate in and destroy p53-deficient tumor cells while sparing normal tissue. Tislelizumab is a humanized IgG4 monoclonal antibody that targets the Programmed Cell Death Protein 1 (PD-1) receptor, blocking its interaction with PD-L1 and PD-L2 to enhance the anti-tumor immune response. Lenvatinib is a multi-targeted tyrosine kinase inhibitor that inhibits the vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET. The combination aims to leverage direct viral oncolysis, immune checkpoint blockade, and anti-angiogenic activity to improve outcomes in advanced HCC. This specific regimen is currently being evaluated in a Phase 2 study sponsored by The First Affiliated Hospital of Bengbu Medical University.
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