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Herpes simplex virus type\u20101 (HSV\u20101) has shown strong promise for treating various solid tumors and has been approved to treat melanoma and glioma in human patients. Previously, we reported the generation of an engineered HSV\u20101 vaccine strain VC2, which has shown exceptional promise as an oncolytic and immunotherapeutic virus. In the present work, we engineered VC2 to constitutively express the murine granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF) gene inserted in place of HSV\u20101 Glycoprotein C (gC). We tested the efficacy of VC2\u2010GMCSF for its ability to generate antitumor response in the 4T1 stage four metastatic breast cancer mouse model. GM\u2010CSF expression enhanced VC2 viral replication and infectious virus production. Tumors formed after 7 days of engraftment in the mammary fat pad of Balb\/CJ mice were treated by injecting ~5\u2009\u00d7\u200910<jats:sup>4<\/jats:sup> plaque forming units (PFU) of VC2\/VC2\u2010GMCSF once. Intratumor treatment did not appreciably reduce average primary tumor sizes. However, metastatic foci were significantly reduced in mice lungs treated with VC2\u2010GMCSF compared to VC2 or mock treatment. VC2\u2010GMCSF intratumoral treatment induced a stronger intratumor T cell infiltration but not an increased cytotoxic activity. A significant T cell infiltration was observed in the metastatic areas in VC2\u2010GMCSF treated animals, which was associated with reduced pro\u2010tumor marker PDL1 and VEGF gene expression. These results show that constitutive expression of GM\u2010CSF enhanced the overall efficacy of VC2 for OVT. VC2\u2010GMCSF holds promise as oncolytic and immunotherapeutic virotherapy for breast and other cancers.<\/jats:p>","DOI":"10.1002\/jmv.70220","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T12:49:35Z","timestamp":1739278175000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Novel Oncolytic Herpes Simplex Virus Type\u20101 (HSV\u20101) Vaccine Strain VC2 Constitutively Expressing GM\u2010CSF Causes Increased Intratumoral T Cell Infiltration and Inhibition of Tumor Metastasis in the 4T1\/Balb\/c Mouse Model of Stage Four Breast Cancer"],"prefix":"10.1002","volume":"97","author":[{"given":"Rafiq","family":"Nabi","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences Louisiana State University School of Veterinary Medicine Baton Rouge Louisiana USA"},{"name":"Division of Biotechnology and Molecular Medicine School of Veterinary Medicine Baton 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