Department of Immunology, Cancer Institute and Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Gene Ther. 2012 Dec;19(12):1187-95. doi: 10.1038/gt.2011.197. Epub 2011 Dec 15.
DNA vaccination is an attractive approach for eliciting antigen-specific immunity. In this study, we used magnetosomes (bacterial magnetic particles, BMPs) as carriers of a recombinant DNA composed of a secondary lymphoid tissue chemokine, human papillomavirus type E7 (HPV-E7) and Ig-Fc fragment (pSLC-E7-Fc) to generate a gene vaccine (BMP-V) for tumour immunotherapy. The results indicate that BMPs linked to DNA more efficiently in phosphate-buffered saline (pH=4-5) than in physiological saline. Efficient transfection of BMP-V in vitro and in vivo was achieved when a 600-mT static magnetic field was applied for 10 min. In a mouse tumour model, subcutaneous injection of BMP-V (5 μg, × 3 at 4-day intervals) plus magnetic exposure elicited systemic HPV-E7-specific immunity leading to significant tumour inhibition. The treated mice tolerated BMP-V immunisation well with no toxic side effects, as shown by histopathological examinations of major internal organs. Taken together, these results suggest that BMP can be used as a gene carrier to elicit a systemic immune response.
DNA 疫苗接种是一种有吸引力的方法,可以引起抗原特异性免疫。在这项研究中,我们使用磁铁矿(细菌磁性颗粒,BMP)作为由二次淋巴组织趋化因子、人乳头瘤病毒 E7 型(HPV-E7)和 Ig-Fc 片段(pSLC-E7-Fc)组成的重组 DNA 的载体,以产生用于肿瘤免疫治疗的基因疫苗(BMP-V)。结果表明,BMP 在 pH=4-5 的磷酸盐缓冲盐水(phosphate-buffered saline,PBS)中与 DNA 的结合效率高于生理盐水中的结合效率。当施加 600-mT 的静态磁场 10 分钟时,BMP-V 在体外和体内的有效转染得以实现。在小鼠肿瘤模型中,皮下注射 BMP-V(5μg,×3,间隔 4 天)加磁场暴露可引起全身 HPV-E7 特异性免疫,从而显著抑制肿瘤。如对主要内脏器官的组织病理学检查所示,接受 BMP-V 免疫接种的小鼠耐受良好,没有毒性副作用。总之,这些结果表明,BMP 可用作基因载体来引发全身免疫反应。