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Adenovirus-mediated CCL20/IL-15 gene transfer enhances antitumor immunity in mice |
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| Authors: | Guang-yao Liu Qiu-ying Jia Zhi-jie Li Ya-gang Li Meng-meng Zhang Ming-yuan Liu Xue-lin Wang Yang Li |
| Affiliation: | 1. Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China;2. State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China;3. Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130033, PR China;4. Fourth Hospital of Jilin University, Changchun 130062, PR China;5. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, PR China |
| 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: | CCL20 IL-15 Bicistronic adenovirus Chemokines Cancer immunotherapy |
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