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Transformed tumor cells permissive for CF33 vaccinia replication represent the cellular target for the CF33 oncolytic virus platform, a chimeric orthopoxvirus developed at City of Hope (O'Leary et al., 2020, J. Immunother. Cancer). These cells are characterized by dysregulated signaling pathways, such as impaired Type I interferon responses and overactive growth signaling, which create an environment conducive to selective viral entry and replication (Warner et al., 2020, Mol. Ther. Oncolytics). CF33 is engineered to be highly potent against a wide range of solid tumors while sparing healthy tissues, as demonstrated in preclinical models of colorectal and pancreatic cancer (Imugene, 2024). Upon infection, the virus replicates within the transformed cell, eventually causing oncolysis and the release of progeny virions to infect adjacent cells. This process also liberates tumor-associated antigens and danger signals, which recruit and activate the host's immune system to target distant metastases (ClinicalTrials.gov, NCT04398147). Some variants of the virus, such as CF33-hNIS (Vaxinia), allow for non-invasive imaging of viral replication via the human sodium-iodide symporter (hNIS) biomarker. Overall, these permissive cells serve as both a factory for viral production and a focal point for initiating a systemic anti-tumor immune response.
Oncolytic viral replication leading to direct cell lysis and the release of tumor-associated antigens, which stimulates a systemic anti-tumor immune response.
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