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

T. Y. Weng, M. C. Yen, C. T. Huang, J. J. Hung, Y. L. Chen, W. C. Chen, C. Y. Wang, J. Y. Chang, M. D. Lai

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)888-896
Number of pages9
JournalGene Therapy
Volume21
Issue number10
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Experimental Neoplasms
Molecular Targeted Therapy
Proto-Oncogene Proteins p21(ras)
Genetic Vectors
DNA Vaccines
Doxycycline
Transgenic Mice
Lung Neoplasms
Plasmids
Mutation
Therapeutic Uses
Neoplasms
Lung
Oncogenes
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Sarcoma
Vaccination

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Weng, T. Y., Yen, M. C., Huang, C. T., Hung, J. J., Chen, Y. L., Chen, W. C., ... Lai, M. D. (2014). DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model. Gene Therapy, 21(10), 888-896. https://doi.org/10.1038/gt.2014.67

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

In: Gene Therapy, Vol. 21, No. 10, 01.01.2014, p. 888-896.

Research output: Contribution to journalArticle

Weng, TY, Yen, MC, Huang, CT, Hung, JJ, Chen, YL, Chen, WC, Wang, CY, Chang, JY & Lai, MD 2014, 'DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model', Gene Therapy, vol. 21, no. 10, pp. 888-896. https://doi.org/10.1038/gt.2014.67
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. / DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model. In: Gene Therapy. 2014 ; Vol. 21, No. 10. pp. 888-896.
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