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Development and preclinical evaluation of ovNDV-28: a chimeric Newcastle disease virus expressing human IL-2 for cancer therapy

Cancer Gene Therapy (2025)Cite this article

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Abstract

Newcastle disease virus (NDV) is a promising oncolytic virus, yet requires further optimization. In this study, we engineered an F-gene-chimeric NDV expressing human Interleukin 2 (hIL-2) to enhance the oncolytic efficacy of the NDV Clone30 strain. This recombinant virus, designated ovNDV-28, was then produced in suspension-cultured HEK293 cells. The therapeutic potential of ovNDV-28 was evaluated across multiple cancer cell lines, as well as in the HuH-7 xenograft and B16-F0 syngeneic models. Both in vitro and in vivo results demonstrated that ovNDV-28 significantly improved tumor growth suppression compared to the wild-type NDV. Flow cytometry revealed notable increases in tumor-infiltrating CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, and CD3⁻CD49b⁺ cells, along with elevated expression levels of IFN-γ, TNF-α, perforin, and Granzyme B within tumor tissue. Comprehensive toxicological assessments conducted on B16-F0 tumor-bearing mice involved intratumoral administration of ovNDV-28 at doses of 1.12 × 10⁶ or 1.46 × 10⁷ PFU/mouse every other day for 14 days. No ovNDV-28-related biochemical, hematological, or histopathological abnormalities were observed. The virus was detected in tumor tissue, mesenteric lymph nodes, abdominal adipose tissue, brain, and biceps femoris, without evidence of blood circulation or viral shedding. This study systematically demonstrates the efficacy, safety, and pharmacokinetics of ovNDV-28, supporting its potential for clinical translation.

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Fig. 1: Generation of an oncolytic NDV virus ovNDV-28 expressing hIL-2 gene.
Fig. 2: Cytotoxicity of ovNDV-28 against various cells in vitro.
Fig. 3: ovNDV-28 exhibits potent antitumor efficacy without detectable toxicity in human tumor xenograft models.
Fig. 4: ovNDV-28 exhibits potent antitumor efficacy in B16-F0 tumor-bearing mice.
Fig. 5: ovNDV-28 shows enhanced antitumor immunity.
Fig. 6: Effects of multiple intratumoral injections of ovNDV-28 on physiological parameters in B16-F0 tumor-bearing C57BL/6J mice.
Fig. 7: Effects of multiple intratumoral injections of ovNDV-28 on hematological and biochemical parameters in B16-F0 tumor-bearing C57BL/6J mice.

Data availability

The data and materials supporting this article are available upon reasonable request.

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Acknowledgements

This work was supported by Jiangsu Kanion Pharmaceutical Co., Ltd., the Innovation and Entrepreneurship Programs of Jiangsu Province and of Lianyungang City, and the Science and Technology Project of Jiangsu Province (Social Development Category, No. BE2022769).

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Authors and Affiliations

  1. College of Life Science, Northeast Agricultural University, Harbin, China

    Tianyan Liu & Deshan Li

  2. Jiangsu Kanion Pharmaceutical Co., Ltd., Jiangning Industrial City, Economic and Technological Development Zone, Jiangsu Lianyungang, China

    Tianyan Liu, Zhihang Liu, Dan Yu, Chengkai Yin, Yu Zhang, Yating Zhang, Hongna Chen, Chenfeng Zhang, Xu Li, Jiarui Yang, Shishi Liu, Zhenzhong Wang & Deshan Li

  3. State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, School of Pharmaceutical Sciences, Peking University, Beijing, China

    Shan Jiang

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Contributions

Tianyan Liu: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Project administration, Writing-original draft, Visualization. Zhihang Liu: Project administration, Methodology, Investigation, Software. Dan Yu: Project administration, Methodology, Investigation, Validation. Shan Jiang: Methodology, Validation, Software. Chengkai Yin: Methodology, Investigation. Yu Zhang: Methodology, Investigation. Yating Zhang: Methodology, Investigation. Hongna Chen: Methodology, Investigation. Xu Li: Resources, Funding acquisition. Chenfeng Zhang: Validation, Resources. Jiarui Yang: Investigation. Shishi Liu: Investigation. Zhenzhong Wang: Methodology, Validation, Project administration, Funding acquisition, Data curation. Deshan Li: Conceptualization, Methodology, Validation, Supervision, Resources, Data curation.

Corresponding authors

Correspondence to Zhenzhong Wang or Deshan Li.

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All animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC, S-ACU22-2110, KAI2203P-P001, 10008-22017) and adhered to the guidelines established by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).

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Liu, T., Liu, Z., Yu, D. et al. Development and preclinical evaluation of ovNDV-28: a chimeric Newcastle disease virus expressing human IL-2 for cancer therapy. Cancer Gene Ther (2025). https://doi.org/10.1038/s41417-025-00981-x

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