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DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model

Gene Therapy volume 21, pages 888–896 (2014)Cite this article

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Abstract

Mutant Kras (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is observed in more than 20% of non-small-cell lung cancers; however, no effective Kras target therapy is available at present. The Kras DNA vaccine may represent as a novel immunotherapeutic agent in lung cancer. In this study, we investigated the antitumor efficacy of the Kras DNA vaccine in a genetically engineered inducible mouse lung tumor model driven by KrasG12D. Lung tumors were induced by doxycycline, and the therapeutic effects of Kras DNA vaccine were evaluated with delivery of KrasG12D plasmids. Mutant KrasG12D DNA vaccine significantly decreased the tumor nodules. A dominant-negative mutant KrasG12DN17, devoid of oncogenic activity, achieved similar therapeutic effects. The T-helper 1 immune response was enhanced in mice treated with Kras DNA vaccine. Splenocytes from mice receiving Kras DNA vaccine presented an antigen-specific response by treatment with peptides of Kras but not Hras or OVA. The number of tumor-infiltrating CD8+ T cells increased after Kras vaccination. In contrast, Kras DNA vaccine was not effective in the lung tumor in transgenic mice, which was induced by mutant L858R epidermal growth factor receptor. Overall, these results indicate that Kras DNA vaccine produces an effective antitumor response in transgenic mice, and may be useful in treating lung cancer-carrying Ras mutation.

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Acknowledgements

This study is supported by the Grants NSC-102-2325-B-006-007 (from National Science Council, Taiwan) and NHRI-EX100-9927B1 (from National Health Research Institute, Taiwan) to MDL. To establish Centers of Excellence for Cancer Research in Taiwan, funding was provided by the Grant DOH101-TD-C-111-003 (Department of Health, Executive Yuan, Taiwan).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC,

    T-Y Weng, M-C Yen, C-T Huang, W-C Chen, C-Y Wang & M-D Lai

  2. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC,

    T-Y Weng, M-C Yen, W-C Chen, C-Y Wang & M-D Lai

  3. Center for Infectious Diseases and Signal Research, National Cheng Kung University, Tainan, Taiwan, ROC,

    M-C Yen & M-D Lai

  4. Institute of Bioinformatics and Biosignal Transduction, College of Life Science, National Cheng Kung University, Tainan, Taiwan, ROC,

    J-J Hung

  5. Department of Senior Citizen Services Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, ROC

    Y-L Chen

  6. National Institute of Cancer Research, National Health Research Institute, Tainan, Taiwan, ROC

    J-Y Chang

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Weng, TY., Yen, MC., Huang, CT. et al. DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model. Gene Ther 21, 888–896 (2014). https://doi.org/10.1038/gt.2014.67

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