Acta Pharmacologica Sinica (2009) 30: 355-363; doi: 10.1038/aps.2009.4

 
Original Article
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Immunotherapy of tumors with recombinant adenovirus encoding macrophage inflammatory protein 3β  induces tumor-specific immune response in immunocompetent tumor-bearing mice
 

Jian-mei HOU1, Xia ZHAO2, Ling TIAN1, Gang LI1, Ru ZHANG1, Bing YAOv, Hong-xin DENG1, Jin-liang YANG1, Yu-quan WEI1*

1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University; 2Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China

 

Aim: Tumor immunotherapy aims at activating the body’s own immune system to fight an existing tumor.  Effective antitumor responses require tumor antigens to be presented to lymphocytes.  We aimed to test the hypothesis that intratumoral administration of recombinant adenovirus encoding MIP3β would induce antitumor immunity by attracting and facilitating the interaction between lymphocytes and dendritic cells.

Methods: A recombinant adenovirus encoding microphage inflammatory protein 3β (AdMIP3β) was constructed.  The antitumor activity of AdMIP3β in BALB/c and C57BL/6 mice bearing CT26 colon adenocarcinoma and Lewis lung cancer was evaluated. 

Results: Immunotherapy with AdMIP3β resulted in significant inhibition of tumor growth and prolonged survival of tumor-bearing mice.  Tumor-specific immune responses elicited by AdMIP3β include MHC class I-dependent CD8+ CTL-mediated immune response and IFN-γ response. Immunohistochemical staining demonstrated numerous CD11c+ cells and CD3+ T lymphocytes within tumor tissues of AdMIP3β-treated mice.  These findings suggest that the mechanism of specific antitumor immunity induced by AdMIP3β may be involved in the chemoattraction of both T lymphocytes and DCs to the tumor site and thus facilitate the process of antigen capture and mature DC to prime naive T cells.   

Conclusion: The present study may be important in the exploration of the potential application of AdMIP3β in the treatment of a broad spectrum of tumors.

 

Keywords: chemokines; cytotoxicity; tumor immunity

 
This work was supported by the National Basic Research Program of China (No 2004CB518800, 2004CB518807), the projects of National Natural Science Foundation of China, and the National 863 Project.
 

* Correspondence to Dr Yu-Quan WEI.
E-mail yuquawei@vip.sina.com
Received 2008-08-30   Accepted 2009-01-06

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