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      Apoptotic activity of Newcastle disease virus in comparison with nisin A in MDA-MB-231 cell line

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          Abstract

          Given the development of drug-resistant cancer cells, designing alternative approaches for cancer treatment seems essential. In this study, we evaluated the anti-tumor effects of nisin A and Newcastle disease virus (NDV) on triple-negative MDA-MB-231 cell line. The MDA-MB-231 cell line was separately and in combination subjected to the different concentrations of a Vero-adapted NDV (JF820294.1) and nisin A. The oncolytic effects of these treatments were analyzed by different cytotoxic and apoptosis techniques including trypan blue staining, MTT assay, acridine orange (EB/AO) staining, colony assay and flow cytometry over time. Nisin A at doses of more than 20.00 μg mL -1 could represent the anti-viral effects and interfere with the oncolytic activity of NDV. Moreover, the analyses indicated that the anti-proliferative and cytotoxic features of combination therapy were stronger than those of individual NDV groups. However, the most apoptotic effect was seen in NDV experimental groups. Taken together, the results from cytotoxicity tests, flow cytometry and colony assay showed that either of the oncolytic agents had significant effects at low concentrations 72 hr post-treatment. Thereby, they had the potential to be used as new approaches in cancer treatment.

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          Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy.

          Preexisting lymphocytic infiltration of tumors is associated with superior prognostic outcomes in a variety of cancers. Recent studies also suggest that lymphocytic responses may identify patients more likely to benefit from therapies targeting immune checkpoints, suggesting that therapeutic efficacy of immune checkpoint blockade can be enhanced through strategies that induce tumor inflammation. To achieve this effect, we explored the immunotherapeutic potential of oncolytic Newcastle disease virus (NDV). We find that localized intratumoral therapy of B16 melanoma with NDV induces inflammatory responses, leading to lymphocytic infiltrates and antitumor effect in distant (nonvirally injected) tumors without distant virus spread. The inflammatory effect coincided with distant tumor infiltration with tumor-specific CD4(+) and CD8(+) T cells, which was dependent on the identity of the virus-injected tumor. Combination therapy with localized NDV and systemic CTLA-4 blockade led to rejection of preestablished distant tumors and protection from tumor rechallenge in poorly immunogenic tumor models, irrespective of tumor cell line sensitivity to NDV-mediated lysis. Therapeutic effect was associated with marked distant tumor infiltration with activated CD8(+) and CD4(+) effector but not regulatory T cells, and was dependent on CD8(+) cells, natural killer cells, and type I interferon. Our findings demonstrate that localized therapy with oncolytic NDV induces inflammatory immune infiltrates in distant tumors, making them susceptible to systemic therapy with immunomodulatory antibodies, which provides a strong rationale for investigation of such combination therapies in the clinic.
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            Integrating oncolytic viruses in combination cancer immunotherapy

            Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancer-immunity cycle. Oncolytic viruses directly lyse tumour cells, leading to the release of soluble antigens, danger signals and type I interferons, which drive antitumour immunity. In addition, some oncolytic viruses can be engineered to express therapeutic genes or can functionally alter tumour-associated endothelial cells, further enhancing T cell recruitment into immune-excluded or immune-deserted tumour microenvironments. Oncolytic viruses can also utilize established tumours as an in situ source of neoantigen vaccination through cross-presentation, resulting in regression of distant, uninfected tumours. These features make oncolytic viruses attractive agents for combination strategies to optimize cancer immunotherapy.
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              Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.

              Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma.
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                Author and article information

                Journal
                Vet Res Forum
                Vet Res Forum
                VRF
                Veterinary Research Forum
                Urmia University Press (Urmia, Iran )
                2008-8140
                2322-3618
                2023
                15 January 2023
                : 14
                : 1
                : 29-37
                Affiliations
                [1 ] Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran;
                [2 ] Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran;
                [3 ] Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;
                [4 ] Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
                Author notes
                [* ]Correspondence Ali Mohammadi. DVM, PhD, Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. E-mail: mohammad@shirazu.ac.ir
                Article
                10.30466/vrf.2022.542258.3297
                9906615
                36816859
                9ae3c896-d1e5-4e68-89ce-19e4ac27d4be
                © 2023 Urmia University. All rights reserved.

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly. https://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 22 November 2021
                : 13 March 2022
                Categories
                Original Research Article

                breast cancer,newcastle disease virus,nisin a
                breast cancer, newcastle disease virus, nisin a

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