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Updated: Jan 12, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Development and preclinical evaluation of ovNDV-28: a chimeric Newcastle disease virus expressing human IL-2 for
Tianyan Liu1,2, Zhihang Liu2, Dan Yu2
1College of Life Science, Northeast Agricultural University, Harbin, China.
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.
Insights
Engineered Newcastle disease virus (NDV) expressing human Interleukin 2 (hIL-2) demonstrated enhanced oncolytic efficacy and tumor suppression in preclinical models. The novel ovNDV-28 exhibited a favorable safety profile, supporting its potential for clinical translation in cancer therapy.
Area of Science:
- Oncolytic virotherapy
- Immunotherapy
- Viral engineering
Background:
- Newcastle disease virus (NDV) shows promise as an oncolytic agent but requires optimization for enhanced therapeutic effects.
- Engineering NDV to express therapeutic payloads can improve its tumor-targeting and immune-stimulating capabilities.
Purpose of the Study:
- To engineer a novel F-gene-chimeric NDV expressing human Interleukin 2 (hIL-2), designated ovNDV-28, to enhance oncolytic efficacy.
- To evaluate the therapeutic potential, safety, and pharmacokinetics of ovNDV-28 in preclinical cancer models.
Main Methods:
- Recombinant ovNDV-28 was produced in suspension-cultured HEK293 cells.
- In vitro efficacy was assessed in multiple cancer cell lines.
- In vivo studies utilized HuH-7 xenograft and B16-F0 syngeneic models.
- Immunological responses were analyzed via flow cytometry and cytokine/cytotoxicity marker expression.
- Toxicological assessments and pharmacokinetic analyses were performed in B16-F0 tumor-bearing mice.
Main Results:
- ovNDV-28 significantly suppressed tumor growth both in vitro and in vivo compared to wild-type NDV.
- Increased infiltration of CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, and CD3⁻CD49b⁺ cells was observed in tumors.
- Elevated levels of IFN-γ, TNF-α, perforin, and Granzyme B were detected within tumor tissues.
- Toxicological studies revealed no significant abnormalities, indicating a favorable safety profile.
- Pharmacokinetic analysis showed virus presence in tumor tissue and specific organs, without systemic circulation or shedding.
Conclusions:
- The engineered ovNDV-28 demonstrates potent oncolytic activity and robust anti-tumor immune stimulation.
- ovNDV-28 exhibits a promising safety profile and predictable biodistribution in preclinical models.
- These findings support the further clinical development of ovNDV-28 as a novel oncolytic immunotherapy for cancer treatment.
