Recombinant Newcastle disease virus expressing P53 demonstrates promising antitumor efficiency in hepatoma model

Area of Science:

• Oncolytic virotherapy
• Gene therapy
• Cancer research

Background:

• Newcastle disease virus (NDV) is a promising platform for cancer gene therapy.
• The tumor suppressor protein P53 is crucial for cancer surveillance.
• Hepatocellular carcinoma (HCC) remains a significant health concern requiring novel therapeutic strategies.

Purpose of the Study:

• To develop and evaluate a recombinant NDV expressing the human P53 gene (rNDV-P53) as a potential therapeutic agent for hepatoma.
• To assess the efficacy and safety of rNDV-P53 in vitro and in vivo.

Main Methods:

• Human P53 gene was inserted into a lentogenic NDV strain to create rNDV-P53.
• In vitro studies involved assessing viral replication, cell growth suppression, apoptosis, and mitochondrial membrane potential in HepG2 cells.
• In vivo studies utilized tumor-bearing mice treated with rNDV-P53 or a control virus (rNDV), evaluating tumor volume, weight, survival rates, and apoptosis via TUNEL analysis.
• Serum chemistry analysis was performed to assess potential toxicity.

Main Results:

• rNDV-P53 replicated effectively in HepG2 cells without compromising viral kinetics.
• In vitro, rNDV-P53 significantly increased cell growth suppression and apoptosis while decreasing mitochondrial membrane potential.
• In vivo, rNDV-P53 treatment led to a substantial reduction in tumor volume and weight, a significant increase in survival rate (75% vs. 12.5% for rNDV), and elevated tumor apoptosis.
• No significant toxicity was observed in serum chemistry analyses.

Conclusions:

• Recombinant NDV-P53 demonstrates potent anti-tumor activity against hepatoma.
• rNDV-P53 is a safe and effective candidate for hepatocarcinoma therapy.