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Updated: Jun 10, 2026
Rescue of Recombinant Newcastle Disease Virus from cDNA
Published on: October 12, 2013
Engineered newcastle disease virus as an improved oncolytic agent against hepatocellular carcinoma
Jennifer Altomonte1, Sabrina Marozin, Roland M Schmid
1II Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Abstract:
Newcastle disease virus (NDV) is an intrinsically tumor-specific virus, which is currently under investigation as a clinical oncolytic agent. Several clinical trials have reported NDV to be a safe and effective agent for cancer therapy; however, there remains a clear need for improvement in therapeutic outcome. The endogenous NDV fusion (F) protein directs membrane fusion, which is required for virus entry and cell-cell fusion. Here, we report a novel NDV vector harboring an L289A mutation within the F gene, which resulted in enhanced fusion and cytotoxicity of hepatocellular carcinoma (HCC) cells in vitro, as compared with the rNDV/F3aa control virus. In vivo administration of the recombinant vector, termed rNDV/F3aa(L289A), via hepatic arterial infusion in immune-competent Buffalo rats bearing multifocal, orthotopic liver tumors resulted in tumor-specific syncytia formation and necrosis, with no evidence of toxicity to the neighboring hepatic parenchyma. Furthermore, the improved oncolysis conferred by the L289A mutation translated to significantly prolonged survival compared with control NDV. Taken together, rNDV/F(L289A) represents a safe, yet more effective vector than wild-type NDV for the treatment of HCC, making it an ideal candidate for clinical application in HCC patients.
Insights
A modified Newcastle disease virus (NDV) with an L289A mutation shows enhanced oncolytic activity against liver cancer (HCC) in preclinical models. This improved NDV vector offers a promising, safer alternative for HCC therapy.
Area of Science:
- Oncolytic virotherapy
- Viral vector engineering
- Hepatocellular carcinoma (HCC) research
Background:
- Newcastle disease virus (NDV) is an oncolytic virus investigated for cancer therapy.
- Existing NDV therapies show safety but require improved therapeutic outcomes.
- The NDV fusion (F) protein is crucial for viral entry and cell fusion.
Purpose of the Study:
- To engineer a novel NDV vector with enhanced oncolytic capabilities.
- To evaluate the efficacy and safety of the engineered NDV vector in HCC models.
- To assess the impact of an L289A mutation in the F gene on NDV's oncolytic potential.
Main Methods:
- A recombinant NDV vector (rNDV/F3aa(L289A)) with an L289A mutation in the F gene was constructed.
- In vitro studies assessed fusion and cytotoxicity in HCC cells.
- In vivo studies used orthotopic liver tumor models in Buffalo rats, administering the vector via hepatic arterial infusion.
Main Results:
- The L289A mutation enhanced NDV-mediated fusion and cytotoxicity in HCC cells in vitro.
- In vivo, rNDV/F3aa(L289A) induced tumor-specific syncytia formation and necrosis without harming surrounding liver tissue.
- The modified NDV vector significantly improved survival rates in tumor-bearing rats compared to control NDV.
Conclusions:
- The engineered NDV vector, rNDV/F3aa(L289A), demonstrates superior oncolytic efficacy and safety for HCC treatment.
- This enhanced NDV vector represents a promising candidate for clinical application in HCC patients.
- The L289A mutation is a key factor in improving NDV's therapeutic potential against liver cancer.
