ArticlePublished: 04 November 2025Tianyan Liu1,2,Zhihang Liu2,Dan Yu2,Shan Jiang3,Chengkai Yin2,Yu Zhang2,Yating Zhang2,Hongna Chen2,Chenfeng Zhang2,Xu Li2,Jiarui Yang2,Shishi Liu2,Zhenzhong Wang2 &…Deshan Li ORCID: orcid.org/0000-0002-1611-01541,2 Cancer Gene Therapy (2025)Cite this articleSubjectsGenetic engineeringGenetic vectorsTargeted therapiesAbstractNewcastle 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.This is a preview of subscription content, access via your institutionAccess optionsSubscribe to this journalReceive 12 print issues and online access269,00 € per yearonly 22,42 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to full article PDFBuy nowPrices may be subject to local taxes which are calculated during checkoutFig. 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 availabilityThe data and materials supporting this article are available upon reasonable request.ReferencesBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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EBioMedicine. 2019;47:89–97.Article PubMed PubMed Central Google Scholar Download referencesAcknowledgementsThis 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).Author informationAuthors and AffiliationsCollege of Life Science, Northeast Agricultural University, Harbin, ChinaTianyan Liu & Deshan LiJiangsu Kanion Pharmaceutical Co., Ltd., Jiangning Industrial City, Economic and Technological Development Zone, Jiangsu Lianyungang, ChinaTianyan Liu, Zhihang Liu, Dan Yu, Chengkai Yin, Yu Zhang, Yating Zhang, Hongna Chen, Chenfeng Zhang, Xu Li, Jiarui Yang, Shishi Liu, Zhenzhong Wang & Deshan LiState Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaShan JiangAuthorsTianyan LiuView author publicationsSearch author on:PubMed Google ScholarZhihang LiuView author publicationsSearch author on:PubMed Google ScholarDan YuView author publicationsSearch author on:PubMed Google ScholarShan JiangView author publicationsSearch author on:PubMed Google ScholarChengkai YinView author publicationsSearch author on:PubMed Google ScholarYu ZhangView author publicationsSearch author on:PubMed Google ScholarYating ZhangView author publicationsSearch author on:PubMed Google ScholarHongna ChenView author publicationsSearch author on:PubMed Google ScholarChenfeng ZhangView author publicationsSearch author on:PubMed Google ScholarXu LiView author publicationsSearch author on:PubMed Google ScholarJiarui YangView author publicationsSearch author on:PubMed Google ScholarShishi LiuView author publicationsSearch author on:PubMed Google ScholarZhenzhong WangView author publicationsSearch author on:PubMed Google ScholarDeshan LiView author publicationsSearch author on:PubMed Google ScholarContributionsTianyan 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 authorsCorrespondence to Zhenzhong Wang or Deshan Li.Ethics declarationsCompeting interestsThe authors declare no competing interests.Ethics approvalAll 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).Consent for publicationAll authors approved the publication of this article.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Rights and permissionsSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this article