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Here we report that combined therapy with two recombinant variants of the oncolytic vaccinia virus, armed with either herpes simplex virus thymidine kinase (VV-HSVtk) or the interleukin 15 receptor subunit alpha (VV-mIL15R\u03b1), leads to enhanced cytotoxicity and immune stimulation in a murine mammary adenocarcinoma model (4T1). In vitro, VV-HSVtk exhibited dose-dependent cytotoxicity markedly potentiated by ganciclovir (GCV) through HSVtk-mediated phosphorylation into a cytotoxic nucleoside analog, and co-culture of VV-infected tumor cells with donor-derived NK cells further increased oncolytic efficiency. In vivo, combined treatment with VV-HSVtk, VV-mIL15R\u03b1, and GCV resulted in significant tumor regression and extended survival relative to monotherapy controls in 4T1 syngeneic mice. Histological examination revealed increased lymphocytic infiltration at tumor sites and absence of hepatic or splenic toxicity. Together, these data indicate that integrating direct viral cytotoxicity, HSVtk\/GCV-mediated suicide gene therapy, and IL-15-pathway-targeted immunomodulation within an oncolytic vaccinia platform can improve antitumor efficacy in a stringent breast cancer model.<\/jats:p>","DOI":"10.3390\/ijms27135838","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Oncolytic Effect of HSVtk- and IL-15R\u03b1-Armed Vaccinia Viruses Inducing Systemic Antitumor Immunity"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3910-466X","authenticated-orcid":false,"given":"Olga N.","family":"Alekseeva","sequence":"first","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7567-913X","authenticated-orcid":false,"given":"Pavel O.","family":"Vorobyev","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6929-2414","authenticated-orcid":false,"given":"Yasmin","family":"Shakiba","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stepan A.","family":"Ionov","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana S.","family":"Antseva","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia V.","family":"Semenova","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8988-3417","authenticated-orcid":false,"given":"Marat P.","family":"Valikhov","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir A.","family":"Kalsin","sequence":"additional","affiliation":[{"name":"Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies, Federal Medical and Biological Agency, 115682 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-5426","authenticated-orcid":false,"given":"Veronika V.","family":"Vadekhina","sequence":"additional","affiliation":[{"name":"Serbsky National Medical Research Center for Psychiatry and Narcology, Ministry of Health of the Russian Federation, 119034 Moscow, Russia"},{"name":"Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Ostrovitianov Street, 1, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry V.","family":"Kochetkov","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8078-2908","authenticated-orcid":false,"given":"Peter M.","family":"Chumakov","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia V.","family":"Poteryakhina","sequence":"additional","affiliation":[{"name":"Engelhard Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41392-023-01407-6","article-title":"Oncolytic virotherapy: Basic principles, recent advances and future directions","volume":"8","author":"Lin","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alekseeva, O.N., Hoa, L.T., Vorobyev, P.O., Kochetkov, D.V., Gumennaya, Y.D., Naberezhnaya, E.R., Chuvashov, D.O., Ivanov, A.V., Chumakov, P.M., and Lipatova, A.V. (2024). Receptors and Host Factors for Enterovirus Infection: Implications for Cancer Therapy. Cancers, 16.","DOI":"10.3390\/cancers16183139"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41585-021-00483-z","article-title":"Using oncolytic viruses to ignite the tumour immune microenvironment in bladder cancer","volume":"18","author":"Li","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"611","DOI":"10.2217\/imt.15.35","article-title":"Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma","volume":"7","author":"Johnson","year":"2015","journal-title":"Immunotherapy"},{"key":"ref_5","first-page":"823","article-title":"Recombinant Strains of Oncolytic Vaccinia Virus for Cancer Immunotherapy","volume":"88","author":"Shakiba","year":"2023","journal-title":"Biochemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4682","DOI":"10.1038\/s41467-018-06954-z","article-title":"Modifying the cancer-immune set point using vaccinia virus expressing re-designed interleukin-2","volume":"9","author":"Liu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/cgt.2009.85","article-title":"Cytokine-armed vaccinia virus infects the mesothelioma tumor microenvironment to overcome immune tolerance and mediate tumor resolution","volume":"17","author":"Jackaman","year":"2010","journal-title":"Cancer Gene Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12730","DOI":"10.1038\/ncomms12730","article-title":"NK cell development requires Tsc1-dependent negative regulation of IL-15-triggered mTORC1 activation","volume":"7","author":"Yang","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.micinf.2011.10.006","article-title":"The role of interleukin-15 in inflammation and immune responses to infection: Implications for its therapeutic use","volume":"14","author":"Perera","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1016\/j.ymthe.2018.07.013","article-title":"Superagonist IL-15-Armed Oncolytic Virus Elicits Potent Antitumor Immunity and Therapy That Are Enhanced with PD-1 Blockade","volume":"26","author":"Kowalsky","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.omto.2023.05.002","article-title":"Oncolytic therapy with recombinant vaccinia viruses targeting the interleukin-15 pathway elicits a synergistic response","volume":"29","author":"Shakiba","year":"2023","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_12","first-page":"16849","article-title":"Suicide Gene Therapy for Cancer\u2014Current Strategies","volume":"4","author":"Zarogoulidis","year":"2013","journal-title":"J. Genet. Syndr. Gene Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Islam, S., Lee, B., Jiang, F., Kim, E.K., Ahn, S.C., and Hwang, T.H. (2020). Engineering and Characterization of Oncolytic Vaccinia Virus Expressing Truncated Herpes Simplex Virus Thymidine Kinase. Cancers, 12.","DOI":"10.3390\/cancers12010228"},{"key":"ref_14","first-page":"410","article-title":"Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of herpes simplex virus-thymidine kinase","volume":"59","author":"Wildner","year":"1999","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1038\/sj.gt.3300784","article-title":"The bystander effect in the HSVtk\/ganciclovir system and its relationship to gap junctional communication","volume":"5","author":"Touraine","year":"1998","journal-title":"Gene Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11269","DOI":"10.18632\/oncotarget.2579","article-title":"Apoptin enhances the oncolytic properties of vaccinia virus and modifies mechanisms of tumor regression","volume":"5","author":"Kochneva","year":"2014","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"201153","DOI":"10.1016\/j.omton.2026.201153","article-title":"Intravenous oncolytic vaccinia expressing transgenes for enhanced safety, inhibition of shedding, imaging, and systemic cancer immunotherapy","volume":"34","author":"Limsirichai","year":"2026","journal-title":"Mol. Ther. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.7150\/jca.102285","article-title":"Oncolytic Virus Therapy in a New Era of Immunotherapy, Enhanced by Combination with Existing Anticancer Therapies: Turn up the Heat!","volume":"16","author":"Fretwell","year":"2025","journal-title":"J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41392-024-01888-z","article-title":"Cell-cell communication: New insights and clinical implications","volume":"9","author":"Su","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Greco, R., Oliveira, G., Stanghellini, M.T., Vago, L., Bondanza, A., Peccatori, J., Cieri, N., Marktel, S., Mastaglio, S., and Bordignon, C. (2015). Improving the safety of cell therapy with the TK-suicide gene. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00095"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Xie, H., Xi, X., Lei, T., Liu, H., and Xia, Z. (2024). CD8(+) T cell exhaustion in the tumor microenvironment of breast cancer. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1507283"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zonov, E., Kochneva, G., Yunusova, A., Grazhdantseva, A., Richter, V., and Ryabchikova, E. (2016). Features of the Antitumor Effect of Vaccinia Virus Lister Strain. Viruses, 8.","DOI":"10.3390\/v8010020"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"932","DOI":"10.3346\/jkms.2005.20.6.932","article-title":"Increased anti-tumor effect by a combination of HSV thymidine kinase suicide gene therapy and interferon-gamma\/GM-CSF cytokine gene therapy in CT26 tumor model","volume":"20","author":"Yang","year":"2005","journal-title":"J. Korean Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.omtm.2020.01.001","article-title":"Oncolytic Viruses and the Immune System: The Dynamic Duo","volume":"17","author":"Franco","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wu, Y.Y., Sun, T.K., Chen, M.S., Munir, M., and Liu, H.J. (2023). Oncolytic viruses-modulated immunogenic cell death, apoptosis and autophagy linking to virotherapy and cancer immune response. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1142172"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, L., Zuo, M., Zhou, Q., and Wang, Y. (2023). Oncolytic virotherapy in cancer treatment: Challenges and optimization prospects. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1308890"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3390\/biomedicines2020163","article-title":"Tumor Restrictions to Oncolytic Virus","volume":"2","author":"Hinkkanen","year":"2014","journal-title":"Biomedicines"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3892\/ijmm.2025.5612","article-title":"Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review)","volume":"56","author":"Xu","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrclinonc.2017.166","article-title":"Tumour heterogeneity and resistance to cancer therapies","volume":"15","author":"Shaw","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41392-024-01979-x","article-title":"Cold and hot tumors: From molecular mechanisms to targeted therapy","volume":"9","author":"Wu","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Singh, D.D., Haque, S., Kim, Y., Han, I., and Yadav, D.K. (2024). Remodeling of tumour microenvironment: Strategies to overcome therapeutic resistance and innovate immunoengineering in triple-negative breast cancer. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1455211"},{"key":"ref_32","first-page":"5274","article-title":"The \u201cbystander effect\u201d: Tumor regression when a fraction of the tumor mass is genetically modified","volume":"53","author":"Freeman","year":"1993","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"200333","DOI":"10.1016\/j.tvr.2025.200333","article-title":"Oncolytic virus and immunogenic cell death in cancer therapy","volume":"20","author":"Cao","year":"2025","journal-title":"Tumour Virus Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1111\/cas.15843","article-title":"Distinct role of CD8 cells and CD4 cells in antitumor immunity triggered by cell apoptosis using a Herpes simplex virus thymidine kinase\/ganciclovir system","volume":"114","author":"Umegaki","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s12276-022-00736-w","article-title":"The mechanism of HMGB1 secretion and release","volume":"54","author":"Chen","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vultaggio-Poma, V., Sarti, A.C., and Di Virgilio, F. (2020). Extracellular ATP: A Feasible Target for Cancer Therapy. Cells, 9.","DOI":"10.3390\/cells9112496"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cytogfr.2017.08.002","article-title":"Immunobiology of the IL-15\/IL-15Ralpha complex as an antitumor and antiviral agent","volume":"38","author":"Guo","year":"2017","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44123","DOI":"10.18632\/oncotarget.6536","article-title":"Transpresentation of interleukin-15 by IL-15\/IL-15Ralpha mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity","volume":"6","author":"Willemen","year":"2015","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1182\/blood-2003-12-4187","article-title":"Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance","volume":"105","author":"Kobayashi","year":"2005","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"33826","DOI":"10.1074\/jbc.M100209200","article-title":"The absence of activator protein 1-dependent gene expression in THP-1 macrophages stimulated with phorbol esters is due to lack of p38 mitogen-activated protein kinase activation","volume":"276","author":"Carter","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1200\/JCO.2014.57.3329","article-title":"Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer","volume":"33","author":"Conlon","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11254","DOI":"10.1128\/JVI.74.23.11254-11261.2000","article-title":"Characterization of promoter function and cell-type-specific expression from viral vectors in the nervous system","volume":"74","author":"Smith","year":"2000","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1128\/JVI.75.1.11-18.2001","article-title":"Vaccinia virus vectors with an inactivated gamma interferon receptor homolog gene (B8R) are attenuated In vivo without a concomitant reduction in immunogenicity","volume":"75","author":"Verardi","year":"2001","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1136\/gutjnl-2019-319200","article-title":"STAT3 activation through IL-6\/IL-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis","volume":"69","author":"Heichler","year":"2020","journal-title":"Gut"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wu, S.C., and Munger, K. (2021). Role and Clinical Utility of Cancer\/Testis Antigens in Head and Neck Squamous Cell Carcinoma. Cancers, 13.","DOI":"10.20944\/preprints202110.0206.v1"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6757","DOI":"10.1128\/JVI.02570-08","article-title":"Vaccinia virus E3 suppresses expression of diverse cytokines through inhibition of the PKR, NF-kappaB, and IRF3 pathways","volume":"83","author":"Myskiw","year":"2009","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1128\/jvi.67.3.1688-1692.1993","article-title":"The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms","volume":"67","author":"Davies","year":"1993","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Allam, A., Yakou, M., Pang, L., Ernst, M., and Huynh, J. (2021). Exploiting the STAT3 Nexus in Cancer-Associated Fibroblasts to Improve Cancer Therapy. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.767939"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ali, S.R., Jordan, M., Nagarajan, P., and Amit, M. (2022). Nerve Density and Neuronal Biomarkers in Cancer. Cancers, 14.","DOI":"10.3390\/cancers14194817"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1002\/ijc.34658","article-title":"Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression","volume":"153","author":"Treitschke","year":"2023","journal-title":"Int. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5555","DOI":"10.1158\/0008-5472.CAN-21-0839","article-title":"Metastasis-Entrained Eosinophils Enhance Lymphocyte-Mediated Antitumor Immunity","volume":"81","author":"Dulberg","year":"2021","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1186\/s12967-023-04418-7","article-title":"Eosinophils in the tumor microenvironment: Implications for cancer immunotherapy","volume":"21","author":"Ghaffari","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/s41467-024-55455-9","article-title":"Oncolytic reprogramming of tumor microenvironment shapes CD4 T-cell memory via the IL6ra-Bcl6 axis for targeted control of glioblastoma","volume":"16","author":"Grimes","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yin, J., Markert, J.M., and Leavenworth, J.W. (2017). Modulation of the Intratumoral Immune Landscape by Oncolytic Herpes Simplex Virus Virotherapy. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00136"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Franks, M.L., An, J.H., and Leavenworth, J.W. (2024). The Role of Natural Killer Cells in Oncolytic Virotherapy: Friends or Foes?. Vaccines, 12.","DOI":"10.3390\/vaccines12070721"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tosic, V., Thomas, D.L., Kranz, D.M., Liu, J., McFadden, G., Shisler, J.L., MacNeill, A.L., and Roy, E.J. (2014). Myxoma virus expressing a fusion protein of interleukin-15 (IL15) and IL15 receptor alpha has enhanced antitumor activity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109801"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/cgt.2011.81","article-title":"Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity","volume":"19","author":"Stephenson","year":"2012","journal-title":"Cancer Gene Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e003923","DOI":"10.1136\/jitc-2021-003923","article-title":"Natural killer T cell immunotherapy combined with IL-15-expressing oncolytic virotherapy and PD-1 blockade mediates pancreatic tumor regression","volume":"10","author":"Nelson","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13578-020-00485-1","article-title":"Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells","volume":"10","author":"Zhang","year":"2020","journal-title":"Cell Biosci."},{"key":"ref_60","first-page":"11","article-title":"Comparative efficiency of accessible transfection methods in model cell lines for biotechnological applications","volume":"3","author":"Vorobyev","year":"2022","journal-title":"Bull. RSMU"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1158\/2767-9764.CRC-23-0243","article-title":"Statistical Assessment of Drug Synergy from In Vivo Combination Studies Using Mouse Tumor Models","volume":"3","author":"Mao","year":"2023","journal-title":"Cancer Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T04:15:57Z","timestamp":1783138557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,28]]},"references-count":61,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135838"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135838","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,28]]}}}