DNA-based immunization by in vivo transfection of dendritic cells
DNA-based immunization by in vivo transfection of dendritic cells
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DOI：
10.1038/nm1096-1122
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发表时间：
1996-10-01
期刊：
影响因子：
82.9
通讯作者：
Falo, LD
中科院分区：
文献类型：
--
作者：
Condon, C;Watkins, SC;Falo, LD
以诱导有效的抗原特异性免疫的方式递送抗原是疫苗设计中的一个关键挑战。最佳的抗原提呈是由专业的抗原提呈细胞(APC)介导的，APC能够在T细胞激活所需的共刺激信号的背景下摄取、处理并向T细胞递呈抗原。开发免疫策略以优化树突状细胞(最有效的APC)的抗原提呈，是疫苗设计的合理方法。在这里，我们展示了裸露DNA的皮肤基因免疫导致了强大的、抗原特异性的、细胞毒T淋巴细胞介导的保护性肿瘤免疫。这种免疫方法会导致皮肤来源的树突状细胞的转染，这种细胞定位于引流的淋巴结中。这些观察结果为进一步开发基于DNA的疫苗提供了基础，并证明了在体内进行树突状细胞基因工程的可行性。
Delivery of antigen in a manner that induces effective, antigen-specific immunity is a critical challenge in vaccine design. Optimal antigen presentation is mediated by professional antigen-presenting cells (APCs) capable of taking up, processing and presenting antigen to T cells in the context of costimulatory signals required for T-cell activation. Developing immunization strategies to optimize antigen presentation by dendritic cells, the most potent APCs, is a rational approach to vaccine design. Here we show that cutaneous genetic immunization with naked DNA results in potent, antigen-specific, cytotoxic T lymphocyte-mediated protective tumor immunity. This method of immunization results in the transfection of skin-derived dendritic cells, which localize in the draining lymph nodes. These observations provide a basis for further development of DNA-based vaccines and demonstrate the feasibility of genetically engineering dendritic cells in vivo.