DNA vaccine with α-galactosylceramide at prime phase enhances anti-tumor immunity after boosting with antigen-expressing dendritic cells.
DNA vaccine with α-galactosylceramide at prime phase enhances anti-tumor immunity after boosting with antigen-expressing dendritic cells.
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DOI：
10.1016/j.vaccine.2010.08.079
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发表时间：
2010-10-21
期刊：
影响因子：
5.5
通讯作者：
Park, Yeong-Min
中科院分区：
文献类型：
--
作者：
Kim, Daejin;Hung, Chien-Fu;Wu, T. -C.;Park, Yeong-Min
DNA疫苗为细胞毒性T淋巴细胞（CTL）的产生提供了一种有希望的新方法。DNA疫苗确实有一些缺点，包括免疫原性差和致癌基因表达。我们使用自然杀伤t细胞（NKT）配体α-半乳糖神经酰胺（α-GalCer）作为初始DNA疫苗接种的佐剂；并使用强效免疫刺激肿瘤抗原表达树突状细胞（dc）作为加强疫苗接种。一种表达人乳头瘤病毒（HPV） 16型E7的DNA疫苗（pcDNA3-CRT/E7）在起始期与α-GalCer结合，在接种小鼠体内产生的E7特异性CD8+ t细胞数量高于增强期疫苗。因此，在α-GalCer存在的情况下启动DNA疫苗，并用e7脉冲DC-1增强，可显著增强e7特异性CD8+效应细胞和记忆t细胞，并显著提高免疫小鼠对表达e7肿瘤模型（TC-1）的治疗和预防作用。我们的研究结果表明，DNA疫苗与α-GalCer联合可以进一步增强表达抗原的DC-based疫苗的效力，从而产生抗肿瘤免疫。
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 α-galactosylceramide (α-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 α-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 α-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 α-GalCer could be further enhanced by boosting with an antigen-expressing DC-based vaccine to generate anti-tumor immunity.
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