J Breast Cancer.
2023 Apr;26(2):186-200. 10.4048/jbc.2023.26.e9.
Inhibition of Tumor Growth and Metastasis by Newcastle Disease Virus Strain P05 in a Breast Cancer Mouse Model
- Ortega-Rivera OA
1,2 - Gallegos-Alcalá P1
- Jiménez M1
- Quintanar JL3
- Torres-Juarez F4
- Rivas-Santiago B4
- Toro-Arreola Sd5,6
- Salinas E1
- Affiliations
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- 1Department of Microbiology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes, Mexico
- 2Department of NanoEngineering, University of California San Diego, La Jolla, USA
- 3Department of Physiology and Pharmacology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes, Mexico
- 4Medical Research Unit-Zacatecas, Mexican Institute for Social Security (IMSS), Zacatecas, Mexico
- 5Department of Physiology, CUCS, University of Guadalajara, Guadalajara, Mexico
- 6Institute of Research in Chronic Degenerative Diseases, Department of Molecular Biology and Genomic, CUCS, University of Guadalajara, Guadalajara, Mexico
- KMID: 2542002
- DOI: http://doi.org/10.4048/jbc.2023.26.e9
Abstract
- Purpose
Conventional therapies and surgery remain the standard treatment for breast cancer. However, combating the eventual development of metastasis is still a challenge. Newcastle disease virus (NDV) is one of the various species of viruses under clinical evaluation as a vector for oncolytic, gene-, and immune-stimulating therapies. The purpose of this study was to evaluate the antitumor activity of a recombinant NDV (rNDV-P05) in a breast cancer murine model.
Methods
Tumors were induced by injecting the cellular suspension (4T1 cell line) subcutaneously. The virus strain P05 was applied three times at intervals of seven days, starting seven days after tumor induction, and was completed 21 days later. Determination of tumor weight, spleen index, and lung metastasis were done after sacrificing the mice. Serum levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, and TNF-related apoptosis-inducing ligand (TRAIL) were quantified by enzyme-linked immunosorbent assay. CD8+ infiltrated cells were analyzed by immunofluorescence.
Results
rNDV-P05 showed a route-of-administration-dependent effect, demonstrating that the systemic administration of the virus significantly reduces the tumor mass and volume, spleen index, and abundance of metastatic clonogenic colonies in lung tissue, and increases the inhibition rate of the tumor. The intratumoral administration of rNDV-P05 was ineffective for all the parameters evaluated. Antitumor and antimetastatic capability of rNDV-P05 is mediated, at least partially, through its immune-stimulatory effect on the upregulation of TNF-α, TRAIL, IFN-α, and IFN-γ, and its ability to recruit CD8+ T cells into tumor tissue.
Conclusion
Systemic treatment with rNDV-P05 decreases the tumoral parameters in the breast cancer murine model.
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