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Journal of Virology, September 2007, p. 9502-9511, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00208-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Local Expression of Secondary Lymphoid Tissue Chemokine Delivered by Adeno-Associated Virus within the Tumor Bed Stimulates Strong Anti-Liver Tumor Immunity{triangledown}

Chun-min Liang,1,2 Cui-ping Zhong,1 Rui-xia Sun,2 Bin-bin Liu,2 Cheng Huang,2 Jie Qin,1 Shuang Zhou,1 Junling Shan,1 Yin-kun Liu,2 and Sheng-long Ye2*

Department of Anatomy and Histology and Embryology, Shanghai Medical College, Fudan University, 200032 Shanghai, People's Republic of China,1 Liver Cancer Institute of Zhongshan Hospital, Fudan University, 200032 Shanghai, People's Republic of China2

Received 30 January 2007/ Accepted 30 May 2007

Development of an effective antitumor immune response depends on the appropriate interaction of effector and target cells. Thus, the expression of chemokines within the tumor may induce a more potent antitumor immune response. Secondary lymphoid tissue chemokine (SLC) is known to play a critical role in establishing a functional microenvironment in secondary lymphoid tissues. Its capacity to attract dendritic cells (DCs) and colocalize them with T cells makes it a good therapeutic candidate against cancer. In this study, we used SLC as a treatment for tumors established from a murine hepatocellular carcinoma model. SLC was encoded by recombinant adeno-associated virus (rAAV), a system chosen for the low host immunity and high efficiency of transduction, enabling long-term expression of the gene of interest. As a result, rAAV-SLC induced a significant delay of tumor progression, which was paralleled by a profound infiltration of DCs and activated CD4+ T cells and CD8+ T cells (CD3+ CD69+ cells) into the tumor site. In addition, rAAV-SLC treatment was also found to reduce tumor growth in nude mice, most likely due to inhibition of neoangiogenesis. In conclusion, local expression of SLC by rAAV represents a promising approach to induce immune-mediated regression of malignant tumors.

* Corresponding author. Mailing address: Liver Cancer Institute of Zhongshan Hospital, Fudan University, 200032 Shanghai, People's Republic of China. Phone: 86 21 64041990 2150. Fax: 86 21 64037181. E-mail: slye{at}shmu.edu.cn

{triangledown} Published ahead of print on 13 June 2007.

Journal of Virology, September 2007, p. 9502-9511, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00208-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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