title: DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model.
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.
authors: 1] Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC [2] Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: T-Y
authors: TY
authors: Weng
authors: 1] Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC [2] Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC [3] Center for Infectious Diseases and Signal Research, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: M-C
authors: MC
authors: Yen
authors: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: C-T
authors: CT
authors: Huang
authors: Institute of Bioinformatics and Biosignal Transduction, College of Life Science, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: J-J
authors: JJ
authors: Hung
authors: Department of Senior Citizen Services Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, ROC.
authors: Y-L
authors: YL
authors: Chen
authors: 1] Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC [2] Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: W-C
authors: WC
authors: Chen
authors: 1] Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC [2] Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: C-Y
authors: CY
authors: Wang
authors: National Institute of Cancer Research, National Health Research Institute, Tainan, Taiwan, ROC.
authors: J-Y
authors: JY
authors: Chang
authors: 1] Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC [2] Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC [3] Center for Infectious Diseases and Signal Research, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: M-D
authors: MD
authors: Lai
mesh_terms: D000818:Animals; D004318:Doxycycline; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009154:Mutation; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000276:immunology / Q000628:therapy; D010957:Plasmids / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D019444:Vaccines, DNA; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D004318:Doxycycline