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oncoVV-AVL is a genetically modified oncolytic vaccinia virus engineered to express the lectin from the marine sponge *Aphrocallistes vastus* (AVL). Its primary mechanism involves selective viral replication within cancer cells, leading to cell lysis and stimulation of antitumor immune responses. Its unique features include enhancement of viral replication via reactive oxygen species (ROS) induction, promotion of apoptosis and autophagy in cancer cells, and modulation of the tumor microenvironment to favor immune activation (e.g., M1 macrophage polarization, elevated interferon-γ)[1]. The AVL component appears to potentiate the oncolytic effect by stimulating extracellular signal-regulated kinase (ERK) phosphorylation, thereby increasing viral replication in an ERK-dependent manner[2]. In preclinical models, oncoVV-AVL demonstrated superior antitumor efficacy compared to unarmed oncolytic vaccinia virus or other armed variants, suppressing tumor growth in pancreatic, colorectal, and hepatocellular carcinoma models[1][2][3]. The virus also induces significant production of pro-inflammatory cytokines (e.g., IL-6, IL-8, TNF-α) and alters cancer cell metabolism, notably by inhibiting glucose uptake and promoting lipogenesis and autophagy via the ACSS2/TFEB axis in hepatocellular carcinoma[3][4].
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