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- Title
Activated Local Immunity by CC Chemokine Ligand 19-Transduced Embryonic Endothelial Progenitor Cells Suppresses Metastasis of Murine Ovarian Cancer.
- Authors
HAMANISHI, JUNZO; MANDAI, MASAKI; MATSUMURA, NORIOMI; BABA, TSUKASA; YAMAGUCHI, KEN; SHINGO FUJII; KONISHI, IKUO
- Abstract
Although tumor microenvironments play a key role in successful tumor immunotherapy, effective manipulation of local immunity is difficult because of the lack of an appropriate target system. It is well known that bone marrowderived 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 CD81 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.
- Subjects
CHEMOKINES; OVARIAN cancer; IMMUNOTHERAPY; TUMOR treatment; NEOVASCULARIZATION; LYMPHOCYTES; LABORATORY mice; LABORATORY animals
- Publication
Stem Cells, 2010, Vol 28, Issue 1, p164
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.256