Inhibition of Tumor Growth and Metastasis by Newcastle Disease Virus Strain P05 in a Breast Cancer Mouse Model

Oscar Antonio Ortega-Rivera; Pamela Gallegos-Alcalá; Mariela Jiménez; J. Luis Quintanar; Flor Torres-Juarez; Bruno Rivas-Santiago; Susana del Toro-Arreola; Eva Salinas

doi:10.4048/jbc.2023.26.e9

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저자정보: Oscar Antonio Ortega-Rivera (Department of Microbiology Basic Science Center Autonomous University of Aguascalientes Aguascalientes Mexico.Department of NanoEngineering University of California San Diego La Jolla USA.) Pamela Gallegos-Alcalá (Department of Microbiology Basic Science Center Autonomous University of Aguascalientes Aguascalientes Mexico.) Mariela Jiménez (Department of Microbiology Basic Science Center Autonomous University of Aguascalientes Aguascalientes Mexico.) J. Luis Quintanar (Department of Physiology and Pharmacology Basic Science Center Autonomous University of Aguascalientes Aguascalientes Mexico.) Flor Torres-Juarez (Medical Research Unit-Zacatecas Mexican Institute for Social Security (IMSS) Zacatecas Mexico.) Bruno Rivas-Santiago (Medical Research Unit-Zacatecas Mexican Institute for Social Security (IMSS) Zacatecas Mexico.) Susana del Toro-Arreola (Department of Physiology CUCS University of Guadalajara Guadalajara Mexico.Institute of Research in Chronic Degenerative Diseases Department of Molecular Biology and Genomic CUCS University of Guadala) Eva Salinas (Department of Microbiology Basic Science Center Autonomous University of Aguascalientes Aguascalientes Mexico.)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.26 No.2

발행연도: 2023.4

수록면: 186 - 200 (15page)

DOI: 10.4048/jbc.2023.26.e9

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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.

#Immunotherapy #Neoplasm Metastasis #Neoplasms #Newcastle Disease Virus

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Oscar Antonio Ortega-Rivera

소속기관 Department of Microbiology Basic Science Center Autonomous University of Aguascalientes Aguascalientes Mexico.Department of NanoEngineering University of California San Diego La Jolla USA.