title: Suppression of metastatic murine ovarian cancer cells by transduced embryonic progenitor cells.
abstract: Ovarian cancer is the leading cause of death among gynecological malignancies. Chemotherapy alone is not sufficient to achieve long-term survival of the patient with advanced stage ovarian cancer. Although cancer immune therapy has long been expected as a new modality for ovarian cancer, very few trials have been clinically successful. One of the reasons for the failure in practical immune therapy is the immune-suppressive cancer microenvironment. We have reported that immune-suppressive molecules including PD-L1, Cox or ULBP-2 are expressed in human ovarian cancer, and they suppress local tumor immunity by disturbing CD8+T cell infiltration. Thus, we attempted to develop an immune therapy that can target multiple metastatic foci and increase CD8+T cell infiltration by altering local tumor environment. Endothelial progenitor cells (EPC) were transduced with the chemokine CCL19. When injected intravenously, this "immune-stimulatory EPC" was incorporated efficiently into local tumor vessels, and exerted an anti-tumor effect in a subcutaneous tumor model, a lung metastasis model and a peritoneal dissemination model. The anti-tumor effect was not observed when immunodeficient mice were used for the experiment, suggesting that the effect is mediated by immune cells. These results suggest that EPC are ideal carriers with which to deliver immune-stimulatory signals to multiple remote metastases. Alteration of local immune environment by this method may be used in the future for individualized cancer immune therapy.
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. mandai@kuhp.kyoto-u.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Mandai
authors.forename: Junzo
authors.initials: J
authors.lastname: Hamanishi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Abiko
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Baba
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D000818:Animals; D002460:Cell Line; D054415:Chemokine CCL19 / Q000235:genetics / Q000276:immunology*; D053595:Embryonic Stem Cells / Q000637:transplantation*; D042783:Endothelial Cells / Q000637:transplantation*; D005260:Female; D005822:Genetic Vectors; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D014161:Transduction, Genetic
chemical_list: D054415:Chemokine CCL19