Vaccinia virus-mediated oncolysis (OVV-mediated oncolysis (OVV = oncolytic vaccinia virus))

Vaccinia virus-mediated oncolysis refers to the use of engineered oncolytic vaccinia viruses (OVVs) to selectively infect, replicate within, and lyse cancer cells while stimulating antitumor immunity. OVVs typically enter tumor cells through macropinocytosis rather than specific receptors, replicate in the cytoplasm, and release progeny virions that spread within the tumor. Tumor selectivity arises from tumor-intrinsic defects in antiviral pathways (e.g., attenuated type I interferon signaling) and tumor suppressor alterations, and from viral gene deletions (such as vaccinia thymidine kinase) that restrict replication in normal tissues. Beyond direct oncolysis, OVVs disrupt tumor vasculature and induce immunogenic cell death, releasing tumor-associated antigens and danger signals that activate innate and adaptive immune responses, which can extend to non-injected lesions. Modern OVV platforms are frequently “armed” with transgenes to enhance apoptosis, autophagy, immune stimulation, or local prodrug conversion (e.g., FCU-1 converting 5-fluorocytosine to 5-fluorouracil), and can be designed to locally block immunosuppressive pathways such as TGF-β. OV outcomes reflect a balance among viral replication, host immunity, and tumor growth; combination strategies with immunotherapies and chemotherapies are under active investigation.

Other names

oncolytic vaccinia virusoncolytic vaccinia virotherapyvaccinia oncolytic virusoncolytic poxvirusOVVoncolytic virus therapy using vaccinia

Selective viral replication in tumor cells due to defects in antiviral pathways and tumor suppressor genes (e.g., downregulated type I IFN signaling; alterations in p53, RAS, PTEN), leading to lytic death of infected tumor cells Receptor-independent entry via macropinocytosis; cytoplasmic replication; release and spread of progeny virions to neighboring tumor cells Activation of antitumor immunity through immunogenic cell death with release of tumor-associated antigens, DAMPs, and PAMPs, promoting dendritic cell activation and T cell responses, including abscopal effects Disruption of tumor vasculature through endothelial cell lysis and thrombotic mechanisms, reducing tumor blood supply Transgene-mediated effects: engineered OVVs expressing cytokines or modulators (e.g., GM-CSF analogs, IL-12, IFN-β, TRAIL, SMAC, Beclin-1) to enhance apoptosis, autophagy, or immune stimulation; suicide gene systems (e.g., FCU-1 converting 5-FC to 5-FU) Tumor-localized blockade of immunosuppressive pathways (e.g., engineered oncolytic viruses that block TGF-β within tumors)