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T. Weng



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    P2.05 - Poster Session 2 - Preclinical Models of Therapeutics/Imaging (ID 158)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.05-019 - Therapeutic efficacy of DNA vaccine by targeting the mutant Kras in KrasG12D-induced lung cancer model (ID 3169)

      09:30 - 09:30  |  Author(s): T. Weng

      • Abstract

      Background
      Mutant Kras was observed in more than 20% of non-small cells lung cancers (NSCLC) and represented one of the most dominant oncogene during cancer progression. However, there were fewer effective inhibitors which specific targeting of mutant Kras in clinical trials. The immunotherapeutic effects of Kras DNA vaccine in lung cancer were not well understood.

      Methods
      In this study, we investigated anti-tumor efficacy of mutant Kras DNA vaccine in spontaneous mouse lung tumor model driven by Kras[G12D]. TetO-Kras[G12D] and Scgb1a1-rtTA bitransgenic mice were treated with doxycycline to induce lung tumor for 5 months. To evaluate therapeutic effects of Kras DNA vaccine, bitransgenic mice with lung tumor were treated with wild-type Kras or mutant Kras[G12D] plasmids by skin administration.

      Results
      In this model, we found that skin administration of mutant Kras DNA vaccine had better therapeutic effects compared to control group. Additionally, dominant negative Kras (N17) DNA vaccine significantly decreased tumor nodules on lung in transgenic mice expressed mutant Kras. Th-1 immune response was dramatically enhanced in vaccine-treated mice compared with in control mice.

      Conclusion
      Overall, our results indicated that Kras DNA vaccine produced an effective anti-tumor response. Furthermore, skin administration of Kras DNA vaccine is effective as a potential approach for lung cancer therapy.