Combinational effects of VC2-GMCSF oncolytic virus and paclitaxel in end-stage breast cancer animal model

Resistance and metastasis continue to make breast cancer a clinical challenge. VC2-GM-CSF drives antitumor immunity; paclitaxel remodels tumor environment to boost immune infiltration. Thus, combined use may yield superior therapeutic benefit over the use of either agent alone. This study investigates the potential synergistic interactions of VC2-GM-CSF with paclitaxel using the murine 4T1 breast cancer model in vitro and in vivo. In vitro, 4T1 cells were treated with paclitaxel alone or in combination with VC2-GM-CSF, and cell viability was assessed by MTT assay. Viral entry was quantified using a flow-cytometric assay. We further explored the in vivo antitumor effect of combined VC2-GM-CSF and paclitaxel in an orthotopic 4T1 stage IV metastatic model of breast cancer. Established 4T1 tumors in BALB/c mice were treated intratumorally with VC2-GM-CSF combined with paclitaxel. On day 31, tumors and lungs were collected for histopathological evaluation. Flow cytometric quantification of lymphocytes infiltrating the tumors was performed for CD45 + , CD3 + , CD4 + , and CD8 + cells. The combined treatment was substantially more effective in inducing dose-dependent decreases in the viability of 4T1 cells and cell death than either single therapy in vitro. Flow cytometric entry assays showed that paclitaxel does not impair the entry of VC2-GM-CSF into cancer cells. In vivo, the combination significantly reduced primary tumor growth compared with the control treatment. Flow cytometry and immunohistochemistry analyses indicated increased T-cell infiltration in tumors after combination therapy. Together, these results demonstrate an enhanced antitumor effect resulting from the complementary cytotoxic and immunomodulatory mechanisms of paclitaxel and oncolytic virotherapy.