Gene Therapy advance online publication 8 February 2007; doi: 10.1038/sj.gt.3302893

Mannan-modified adenovirus as a vaccine to induce antitumor immunity
Z-Y Ding1,2, Y Wu1,2, Y Luo1, J-M Su1, Q Li1, X-W Zhang1, J-Y Liu1, Q-M He1, L Yang1, L Tian1, X Zhao1, H-X Deng1, Y-J Wen1, J Li1, B Kang1 and Y-Q Wei1

1Department of Oncology, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, The People's Republic of China

Correspondence: Professor Y-Q Wei, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Chengdu, Sichuan 610041, People's Republic of China. E-mail: yuquawei@vip.sina.com

2These authors contributed equally to this work.

Received 7 July 2006; Revised 1 November 2006; Accepted 6 November 2006; Published online 8 February 2007.

Tumor vaccine is a useful strategy for cancer therapy. However, priming of the immune system requires the relevant antigen to be presented by antigen-presenting cells (APCs). Here, we employed telomerase reverse transcriptase as a model antigen to explore the feasibility of using mannan-modified adenovirus as a tumor vaccine. We found that tumor immunogene therapy with the vaccine was effective at protective antitumor immunity in mice. The antigen-specific cytotoxic T lymphocytes were found in in vitro cytotoxicity assay. The elevation of the killing activity could be abrogated by anti-CD8 or anti-major histocompatibility complex-I antibodies. Adoptive transfer of purified CD8+ cells, and CD4+ cells to a less extent, was effective at antitumor activity. In vivo antitumor activity could be abrogated by depleting CD4+ T lymphocytes. A possible explanation for the antitumor effects may be the antigen was transfered to APCs in the presence of mannan. These observations provide insights into the design of novel vaccine strategies and might be important for the future application of antigens identified in other diseases.

Keywords: gene transfer, adenovirus vector, mannan, tumor vaccine