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

doi:10.1038/gt.2014.67

CNU IR > College of Smart Living > Dept. of Senior Service and Health Management > Periodical Articles > Item 310902800/28545

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/28545

Title:	DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model
Authors:	Weng, T-Y Yen, M-C Huang, C-T Hung, J-J Chen, Y-L Chen, W-C Wang, C-Y Chang, J-Y Lai, M-D
Contributors:	老人服務事業管理系
Keywords:	GROWTH-FACTOR RECEPTOR K-RAS MUTATIONS IMMUNE-RESPONSE GENE GUN IN-VIVO PROGNOSTIC-SIGNIFICANCE INTERFERON-GAMMA DOWN-REGULATION T-LYMPHOCYTES TUMOR-CELLS
Date:	2014-10
Issue Date:	2015-05-06 21:20:08 (UTC+8)
Publisher:	Nature Publishing Group
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 Kras(G12D). Lung tumors were induced by doxycycline, and the therapeutic effects of Kras DNA vaccine were evaluated with delivery of Kras(G12D) plasmids. Mutant Kras(G12D) DNA vaccine significantly decreased the tumor nodules. A dominant-negative mutant Kras(G12D)N17, 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.
Relation:	Gene therapy, v.21 n.10, pp.888-896
Appears in Collections:	[Dept. of Senior Service and Health Management] Periodical Articles

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