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BO-112 + nivolumab is a combination immunotherapy regimen under clinical investigation for the treatment of various solid tumors, including melanoma, basal cell carcinoma, non-small cell lung cancer, and others. BO-112 is a synthetic double-stranded RNA (dsRNA) based on polyinosinic:polycytidylic acid (poly I:C), formulated with the cationic carrier polyethyleneimine to enhance delivery and stability. It acts as a viral mimetic and functions primarily as an immunostimulant by activating innate immune sensors such as Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I protein (RIG-I/DDX58), melanoma differentiation-associated protein 5 (MDA5/IFIH1), and stimulating interferon responses. This leads to increased production of cytotoxic cytokines and activation of antigen-presenting cells, promoting anti-tumor immunity[1][2][3][7]. Nivolumab is a fully human monoclonal antibody targeting programmed cell death protein 1 (PD‑1). By blocking PD‑1 on T-cells, it prevents tumor-mediated immune suppression via PD-L1/PD-L2 ligands expressed on cancer cells, thereby restoring T-cell mediated anti-tumor activity[6][8]. The combination leverages both local innate immune activation by intratumoral BO‑112 and systemic checkpoint inhibition by intravenous nivolumab. Preclinical studies have shown synergistic effects in mouse models; early clinical trials suggest potential benefit in patients with refractory or advanced cancers[3].
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