title: Vaccination with vascular progenitor cells derived from induced pluripotent stem cells elicits antitumor immunity targeting vascular and tumor cells.
abstract: Vaccination of BALB/c mice with dendritic cells (DCs) loaded with the lysate of induced vascular progenitor (iVP) cells derived from murine-induced pluripotent stem (iPS) cells significantly suppressed the tumor of CMS-4 fibrosarcomas and prolonged the survival of CMS-4-inoculated mice. This prophylactic antitumor activity was more potent than that of immunization with DCs loaded with iPS cells or CMS-4 tumor cells. Tumors developed slowly in mice vaccinated with DCs loaded with iVP cells (DC/iVP) and exhibited a limited vascular bed. Immunohistochemistry and a tomato-lectin perfusion study demonstrated that the tumors that developed in the iVP-immunized mice showed a marked decrease in tumor vasculature. Immunization with DC/iVP induced a potent suppressive effect on vascular-rich CMS-4 tumors, a weaker effect on BNL tumors with moderate vasculature, and nearly no effect on C26 tumors with poor vasculature. Treatment of DC/iVP-immunized mice with a monoclonal antibody against CD4 or CD8, but not anti-asialo GM1, inhibited the antitumor activity. CD8(+) T cells from DC/iVP-vaccinated mice showed significant cytotoxic activity against murine endothelial cells and CMS-4 cells, whereas CD8(+) T cells from DC/iPS-vaccinated mice did not. DNA microarray analysis showed that the products of 29 vasculature-associated genes shared between genes upregulated by differentiation from iPS cells into iVP cells and genes shared by iVP cells and isolated Flk-1(+) vascular cells in CMS-4 tumor tissue might be possible targets in the immune response. These results suggest that iVP cells from iPS cells could be used as a cancer vaccine targeting tumor vascular cells and tumor cells.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koido
authors.forename: Masaki
authors.initials: M
authors.lastname: Ito
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sagawa
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.forename: Kazumi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Eijiro
authors.initials: E
authors.lastname: Nagasaki
authors.forename: Shin
authors.initials: S
authors.lastname: Kan
authors.forename: Hideo
authors.initials: H
authors.lastname: Komita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kamata
authors.forename: Sadamu
authors.initials: S
authors.lastname: Homma
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology*; D005354:Fibrosarcoma / Q000628:therapy; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D019496:Cancer Vaccines