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Immunobiology. 2014 Jun;219(6):475-81. doi: 10.1016/j.imbio.2014.02.009. Epub 2014 Mar 1.

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

Author information

1
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China.
2
Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130033, PR China.
3
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
4
Fourth Hospital of Jilin University, Changchun 130062, PR China.
5
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, PR China.
6
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China. Electronic address: myth0317@yeah.net.

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.

KEYWORDS:

Bicistronic adenovirus; CCL20; Cancer immunotherapy; Chemokines; IL-15

PMID:
24657179
DOI:
10.1016/j.imbio.2014.02.009
[Indexed for MEDLINE]
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