title: Anti-tumor effects of inactivated Sendai virus particles with an IL-2 gene on angiosarcoma.
abstract: Cutaneous angiosarcoma is a life-threatening tumor that is resistant to conventional therapies. The therapeutic effects of Sendai virus particles (hemagglutinating virus of Japan envelope: HVJ-E) carrying IL-2 gene (HVJ-E/IL-2) were examined in a mouse model of angiosarcoma. Intra-tumoral injection of HVJ-E/IL-2 effectively inhibited the growth of angiosarcoma cells (ISOS-1) inoculated in mice and improved tumor-free rates. HVJ-E/IL-2 stimulated local accumulation of CD8 (+) T cells and NK cells and reduced regulatory T cells in regional lymph nodes. Notably, the prevalence of myeloid-derived suppressor cells was lower in HVJ-E/IL-2-treated mice than in HVJ-E-treated mice. HVJ-E/IL-2 treatment promoted IFN-γ production from CD8 (+) T cells in response to tumor cells, more significantly than HVJ-E treatment. Greatly improved tumor-free rates were obtained when sunitinib, a tyrosine kinase inhibitor, was administered in combination with HVJ-E/IL-2. Immunogene therapy with HVJ-E/IL-2 with or without sunitinib could be a promising therapeutic option for cutaneous angiosarcoma.
authors.affiliation: Department of Dermatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takehara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Satoh
authors.forename: Aya
authors.initials: A
authors.lastname: Nishizawa
authors.forename: Kazumi
authors.initials: K
authors.lastname: Saeki
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.forename: Mikio
authors.initials: M
authors.lastname: Masuzawa
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.forename: Hiroo
authors.initials: H
authors.lastname: Yokozeki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000166:cytology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006394:Hemangiosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007211:Indoles / Q000008:administration & dosage; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D029082:Sendai virus; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000077210:Sunitinib; D047368:Tumor Burden / Q000187:drug effects; D014771:Virion
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D007376:Interleukin-2; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D007371:Interferon-gamma; D000077210:Sunitinib
keywords: BMDC; Bone marrow-derived dendritic cells; DCs; Dendritic cells; HVJ-E; HVJ-E carrying IL-2 gene; HVJ-E carrying pVAX1 plasmid; HVJ-E/IL-2; HVJ-E/pVAX1; Hemagglutinating virus of Japan envelope; ISOS-1 cells; ISOS-1 cells fused with HVJ-E; ISOS-1/HVJ; MDSC; Myeloid-derived suppressor cells; Regulatory T cells; S.D; Standard deviations; Sunitinib; TILs; Tregs; Tumor infiltrating lymphocytes