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: Yuki Takehara, Takahiro Satoh, Aya Nishizawa, Kazumi Saeki, Masataka Nakamura, Mikio Masuzawa, Yasufumi Kaneda, Ichiro Katayama, Hiroo Yokozeki
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 149 Issue 1 Pg. 1-10 (Oct 2013) ISSN: 1521-7035 [Electronic] United States
• PMID: 23886549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Indoles
• Interleukin-2
• Protein Kinase Inhibitors
• Pyrroles
• Interferon-gamma
• Sunitinib

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Bone Marrow Cells (cytology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dendritic Cells (drug effects, immunology)
• Female
• Hemangiosarcoma (immunology, pathology, therapy)
• Indoles (administration & dosage)
• Interferon-gamma (immunology)
• Interleukin-2 (genetics)
• Lymphocytes (cytology, drug effects, immunology)
• Mice
• Mice, Inbred BALB C
• Oncolytic Virotherapy
• Protein Kinase Inhibitors (administration & dosage)
• Pyrroles (administration & dosage)
• Sendai virus
• Skin Neoplasms (immunology, pathology, therapy)
• Sunitinib
• Tumor Burden (drug effects)
• Virion