Adenovirus-mediated CCL20/IL-15 gene transfer enhances antitumor immunity in mice.

Abstract

The CCL20 chemokine has potent antitumor activities through chemoattracting immature dentritic cells. But the maturation status of tumoral dentritic cells is important limiting factors in DC-based immunity. The endogenous availability of IL-15 was effective in inducing the dentritic cells maturation and IL-15 also shows tumor-specific antitumor activities. We constructed a CCL20/IL-15 bicistronic adenovirus (Ad-CCL20-IL-15) and confirmed its combined antitumor effect in vitro and in vivo. Intratumoral injection of Ad-CCL20-IL-15 into both CT-26 and B16F10 cells resulted in marked reduction of tumor growth in our model. Splenocytes treated by Ad-CCL20-IL-15 developed tumor-specific cytotoxic T cells and IFN-γ secretion could protect mice from rechallenging. This study suggests that CCL20/IL-15 can induce a strong antitumor immune response in tumor tissues and it is a suitable candidate for cancer immunotherapy.

• Authors: Guang-yao Liu, Qiu-ying Jia, Zhi-jie Li, Ya-gang Li, Meng-meng Zhang, Ming-yuan Liu, Xue-lin Wang, Yang Li
• Journal: Immunobiology (Immunobiology) Vol. 219 Issue 6 Pg. 475-81 (Jun 2014) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 24657179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemical References

• CCL20 protein, mouse
• Chemokine CCL20
• Interleukin-15
• Interferon-gamma

Topics

• Adenoviridae (genetics)
• Animals
• Cell Line, Tumor
• Cell Movement
• Chemokine CCL20 (genetics)
• Dendritic Cells (immunology)
• Gene Transfer Techniques
• Genetic Vectors (genetics, therapeutic use)
• Humans
• Immunotherapy
• Interferon-gamma (immunology, metabolism)
• Interleukin-15 (genetics)
• Killer Cells, Natural (immunology)
• Mice
• Mice, Inbred BALB C
• Neoplasms (immunology, therapy)
• T-Lymphocytes, Cytotoxic (immunology)