ORIGINAL RESEARCH article
Front. Med.
Sec. Hepatobiliary Diseases
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1622209
Novel Immune Checkpoint Inhibitor FilC/PD-1 Recombinant Vaccinia Virus Inhibits
Provisionally accepted
- The First Affiliated Hospital of Nanchang University, Nanchang, China
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Background: With few therapeutic choices for advanced stages, hepatocellular carcinoma (HCC) continues to be the primary cause of cancer-related death globally. Though still less than ideal in HCC, immunotherapy-especially immune checkpoint drugs aiming at the PD-1/PD-L1 axis-show promise. Combining direct tumor lysis with immune modulation provides a fresh strategy in oncolytic virotherapy with vaccinia virus. Designed to boost antitumor immunity by dual checkpoint inhibition and oncolysis, this study assessed the efficacy of FilC/PD-1 recombinant vaccinia virus. Methods: Homologous recombination developed a recombinant vaccinia virus expressing FilC and PD-1 inhibitors. We evaluated viral infectivity and replication in HCC cell lines (HepG2, Huh7, Hepa1-6, PLC/PRF/5) and in VERO cells-a non-hepatic kidney epithelial cell line from Chlorocebus sabaeus (African green monkey) commonly used in virology-to assess baseline viral tropism outside the liver. Using BALB/c nude mice (xenograft) and C57BL/6 mice (syngeneic model), in vivo efficacy was assessed in HCC murine models assessing tumor volume reduction, immune cell infiltration, survival rates, and systemic toxicity. Findings: High infection efficiency (88.4% in HepG2), robust viral replication, and substantial oncolytic activity in HCC cells were displayed by the FilC/PD-1 recombinant virus. Compared to the PD-1 inhibitor virus alone, the virus greatly lowered tumor volume (84%) and raised CD8⁺ T cell infiltration (42.8%), hence prolonging survival (68 days). Histopathological study verified low toxicity in main organs. Conclusion: By means of synergistic immune checkpoint inhibition and oncolytic virotherapy, FilC/PD-1 recombinant vaccinia virus significantly increases anti-tumor immunity and slows down HCC growth.
Keywords: Hepatocellular Carcinoma, Oncolytic Virotherapy, immune checkpoint suppression, Vaccinia virus, PD-1, FilC
Received: 02 May 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Wang, Luo, Hu, Du and Xin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Minglong Wang, The First Affiliated Hospital of Nanchang University, Nanchang, China
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