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DNA and adenovirus tumor vaccine expressing truncated survivin generates specific immune responses and anti-tumor effects in a murine melanoma model

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Abstract

Survivin is overexpressed in major types of cancer and is considered an ideal “universal” tumor-associated antigen that can be targeted by immunotherapeutic vaccines. However, its anti-apoptosis function raises certain safety concerns. Here, a new truncated human survivin, devoid of the anti-apoptosis function, was generated as a candidate tumor vaccine. Interleukin 2 (IL-2) has been widely used as an adjuvant for vaccination against various diseases. Meanwhile, the DNA prime and recombinant adenovirus (rAd) boost heterologous immunization strategy has been proven to be highly effective in enhancing immune responses. Therefore, the efficacy of a new cancer vaccine based on a truncated form of survivin, combined with IL-2, DNA prime, and rAd boost, was tested. As prophylaxis, immunization with the DNA vaccine alone resulted in a weak immune response and modest anti-tumor effect, whereas the tumor inhibition ratio with the DNA vaccine administered with IL-2 increased to 89 % and was further increased to nearly 100 % by rAd boosting. Moreover, complete tumor rejection was observed in 5 of 15 mice. Efficacy of the vaccine administered therapeutically was enhanced by nearly 300 % when combined with carboplatin. These results indicated that vaccination with a truncated survivin vaccine using DNA prime–rAd boost combined with IL-2 adjuvant and carboplatin represents an attractive strategy to overcoming immune tolerance to tumors and has potential therapeutic benefits in melanoma cancer.

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Acknowledgments

The authors thank the staff of the National Engineering Laboratory of AIDS Vaccine for reagent ordering and instrument management. The present work was supported by the Central University Basic Research Foundation of China (No. 200903255, 201103179).

Conflict of interest

The authors declare that there are no conflicts of interest in regard to this work.

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Authors and Affiliations

  1. National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun, 130012, China

    Haihong Zhang, Yuqian Wang, Chenlu Liu, Lixing Zhang, Qiu Xia, Yong Zhang, Jiaxin Wu, Chunlai Jiang, Yan Chen, Yongge Wu, Xianghui Yu & Wei Kong

  2. Key Laboratory for Molecular Enzymology and Engineering, College of Life Science, Jilin University, No. 2699, Qianjin Street, Changchun, 130012, China

    Haihong Zhang, Yong Zhang, Jiaxin Wu, Chunlai Jiang, Yan Chen, Yongge Wu, Xianghui Yu & Wei Kong

  3. Sichuan Tumor Hospital and Institute, Chengdu, 610041, China

    Xiao Zha

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  1. Haihong Zhang
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  2. Yuqian Wang
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  3. Chenlu Liu
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  12. Xianghui Yu
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Correspondence to Xianghui Yu or Wei Kong.

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Zhang, H., Wang, Y., Liu, C. et al. DNA and adenovirus tumor vaccine expressing truncated survivin generates specific immune responses and anti-tumor effects in a murine melanoma model. Cancer Immunol Immunother 61, 1857–1867 (2012). https://doi.org/10.1007/s00262-012-1296-3

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  • DOI: https://doi.org/10.1007/s00262-012-1296-3

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