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It is well known that bone marrow-derived endothelial progenitor cells (EPCs) are actively recruited during tumor angiogenesis. Using this feature, we attempted to establish a novel therapeutic modality that targets tumor vessels of multiple metastases using embryonic endothelial progenitor cells (eEPCs) transduced with an immune-activating gene. The eEPCs were retrovirally transduced with the mouse CC chemokine ligand 19 (CCL19) gene, a lymphocyte-migrating chemokine. The mouse ovarian cancer cell line OV2944-HM-1 (HM-1) was inoculated subcutaneously into B6C3F1 mice, along with CCL19-tranduced eEPCs (eEPC-CCL19), resulting in immunologic activity and tumor-inhibitory effects. In this model, eEPC-CCL19 showed tumor repression accompanied by increased tumor-infiltrating CD8+ lymphocytes compared with the control group. In contrast, no tumor repression was observed when the same experiment was done in immunodeficient (SCID) mice, suggesting a crucial role of T-cell function in this system. Next, we established a lung metastasis model by injecting HM-1 cells or B16 melanoma cells via the tail vein. Subsequent intravenous injection of eEPC-CCL19 leads to a decrease in the number of lung metastasis and prolonged survival. Antitumor effects were also observed in a peritoneal dissemination model using HM-1. These results suggest that systemic delivery of an immune-activating signal using EPCs can alter the tumor immune microenvironment and lead to a therapeutic effect, which may provide a novel strategy for targeting multiple metastases of various malignancies.<\/jats:p>","DOI":"10.1002\/stem.256","type":"journal-article","created":{"date-parts":[[2009,11,12]],"date-time":"2009-11-12T19:37:48Z","timestamp":1258054668000},"page":"164-173","source":"Crossref","is-referenced-by-count":46,"title":["Activated Local Immunity by CC Chemokine Ligand 19-Transduced Embryonic Endothelial Progenitor Cells Suppresses Metastasis of Murine Ovarian Cancer \u00a0"],"prefix":"10.1093","volume":"28","author":[{"given":"Junzo","family":"Hamanishi","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, 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