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Modulatory effects of tumor-derived heat shock protein in DNA vaccination against nasopharyngeal carcinoma.

机译:肿瘤衍生的热休克蛋白在针对鼻咽癌的DNA疫苗接种中的调节作用。

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摘要

Use of anti-idiotype antibody vaccines is a promising strategy against tumor, however, their immunogenicity still need to be improved. Heat shock proteins (HSPs) have been shown to act as adjuvants when coadministered with peptides or given as fusion proteins and enhance the vaccination efficiency. To evaluate the enhancement of the potency of anti-idiotype antibody immunogenicity by heat shock protein gp96, C57BL/6 mice were immunized with three intramuscular inoculations of the G22 DNA and/or gp96 DNA vaccine. Control was inoculated with empty plasmid pcDNA3.1. The levels of G22-specific antibody and lymphocyte phenotype were measured by ELISA, fluorescence activated cell sorter (FACS) analysis, respectively. In the tumor protection experiment, the immunized mice were then challenged with CMT-93-G22 cells. The tumor size and the survival time of the animals were compared among these groups. The results showed that the efficacy of G22 DNA vaccine could be enhanced by coadministrating with gp96 DNA which might be relevant with activating CD8(+)T cells. Furthermore, co-injection of G22 DNA with gp96 DNA could prolong the survival time and lessen the tumor size of the CMT-93-G22-bearing mice. Our study demonstrates for the first time that G22+gp96 DNA vaccine can induce comparable G22-specific CD8(+)T cell response and is a promising candidate DNA vaccine for nasopharyngeal carcinoma.
机译:抗独特型抗体疫苗的使用是抗肿瘤的一种有前途的策略,但是,其免疫原性仍需要提高。当与肽共同施用或以融合蛋白形式提供时,热休克蛋白(HSP)已显示出可作为佐剂并提高疫苗接种效率。为了评估热休克蛋白gp96对抗独特型抗体免疫原性的增强作用,对C57BL / 6小鼠进行了三次G22 DNA和/或gp96 DNA疫苗的肌内接种。用空质粒pcDNA3.1接种对照。 G22特异性抗体水平和淋巴细胞表型分别通过ELISA,荧光激活细胞分选仪(FACS)分析进行测量。在肿瘤保护实验中,然后用CMT-93-G22细胞攻击免疫的小鼠。在这些组中比较了动物的肿瘤大小和存活时间。结果表明,与gp96 DNA并用可能会增强G22 DNA疫苗的效力,这可能与激活CD8(+)T细胞有关。此外,将G22 DNA与gp96 DNA一起注射可以延长CMT-93-G22荷瘤小鼠的存活时间并减小其肿瘤大小。我们的研究首次证明,G22 + gp96 DNA疫苗可以诱导可比较的G22特异性CD8(+)T细胞反应,并且是有希望的鼻咽癌候选DNA疫苗。

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