期刊
VACCINE
卷 28, 期 45, 页码 7297-7305出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2010.08.079
关键词
DNA vaccine; alpha-Galactosylceramide; Anti-tumor immunity
资金
- Korean Government [KRF-2008-314-E00195]
- National Cancer Institute SPORE in Cervical Cancer [P50 CA098252, 1 RO1 CA114425-01]
DNA vaccines contribute to a promising new approach for the generation of cytotoxic T lymphocytes (CTL). DNA vaccines do have several disadvantages, including poor immunogenicity and oncogene expression. We used the natural killer T-cell (NKT) ligand alpha-galactosylceramide (alpha-GalCer) as an adjuvant to prime initial DNA vaccination; and used the potent immune-stimulatory tumor antigen-expressing dendritic cells (DCs) as a booster vaccination. A DNA vaccine expressing human papillomavirus (HPV) type 16 E7 (pcDNA3-CRT/E7) was combined with alpha-GalCer at the prime phase, and generated a higher number of E7-specific CD8(+) T-cells in vaccinated mice than vaccine used at boost phase. Therefore, priming with a DNA vaccine in the presence of alpha-GalCer and boosting with E7-pulsed DC-1 led to a significant enhancement of E7-specific CD8(+) effector and memory T-cells as well as significantly improved therapeutic and preventive effects against an E7-expressing tumor model (TC-1) in vaccinated mice. Our findings suggested that the potency of a DNA vaccine combined with alpha-GalCer could be further enhanced by boosting with an antigen-expressing DC-based vaccine to generate anti-tumor immunity. (C) 2010 Elsevier Ltd. All rights reserved.
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