Inhibition of Tumor Growth and Metastasis by Newcastle Disease Virus Strain P05 in a Breast Cancer Mouse Model
Oscar Antonio Ortega-Rivera1,2, Pamela Gallegos-Alcalá1, Mariela Jiménez1
1Department of Microbiology, Basic Science Center, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
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.
Insights
Systemic administration of recombinant Newcastle disease virus (rNDV-P05) effectively reduced breast cancer tumor size and metastasis in mice. This oncolytic virus therapy shows promise by stimulating immune responses and recruiting CD8+ T cells.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Standard breast cancer treatments face challenges with metastasis.
- Newcastle disease virus (NDV) is explored for oncolytic, gene, and immune therapies.
Purpose of the Study:
- Evaluate the antitumor activity of recombinant NDV (rNDV-P05) in a breast cancer mouse model.
- Assess the efficacy of rNDV-P05 in reducing tumor growth and metastasis.
Main Methods:
- Breast cancer tumors induced using 4T1 cell line in mice.
- rNDV-P05 administered systemically or intratumorally three times over 21 days.
- Tumor weight, spleen index, lung metastasis, and immune markers (IFN-α, IFN-γ, TNF-α, TRAIL, CD8+ cells) were analyzed.
Main Results:
- Systemic rNDV-P05 significantly reduced tumor mass, volume, spleen index, and lung metastasis.
- Intratumoral administration of rNDV-P05 showed no significant effect.
- Antitumor and antimetastatic effects were linked to immune stimulation (upregulation of TNF-α, TRAIL, IFN-α, IFN-γ) and CD8+ T cell recruitment.
Conclusions:
- Systemic rNDV-P05 treatment effectively decreased tumoral parameters in a breast cancer mouse model.
- The findings support rNDV-P05 as a potential systemic therapy for breast cancer, leveraging immune stimulation.
