Peptide-Conjugated PAMAM Dendrimer as a Universal DNA Vaccine Platform to Target Antigen-Presenting Cells
Peptide-Conjugated PAMAM Dendrimer as a Universal DNA Vaccine Platform to Target Antigen-Presenting Cells
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DOI：
10.1158/0008-5472.can-11-1766
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发表时间：
2011-12-15
期刊：
影响因子：
11.2
通讯作者：
Serafini, Paolo
中科院分区：
文献类型：
--
作者：
Daftarian, Pirouz;Kaifer, Angel E.;Serafini, Paolo
基于DNA的疫苗由于许多独特的特征而有望优于传统的基于抗原的疫苗。然而，DNA疫苗迄今为止没有达到预期，部分原因是对专职抗原呈递细胞（APC）的靶向性差和免疫原性低。在这项研究中，我们描述了一个新的平台，有效和选择性地交付DNA的APC在体内，提供内在的免疫增强特性。该平台基于第五代聚酰胺胺（G5-PAMAM）树状聚合物（DNA负载表面）与MHC II类靶向肽的缀合，所述MHC II类靶向肽可以在增强其免疫刺激效力的条件下选择性地将这些树状聚合物递送至APC。与该平台缀合的DNA在体外有效转染鼠和人APC。皮下注射DNA-肽-树状聚合物复合物在体内优先转染引流淋巴结中的树突状细胞（DC），促进高亲和力T细胞的产生，并引起对已建立肿瘤的排斥。总之，我们的研究结果表明，PAMAM树枝状聚合物复合物可用于高转染效率和有效靶向体内APC，赋予产生有效DNA疫苗所必需的特性。Cancer Res; 71（24）; 7452-62. (C)2011年AACR。
DNA-based vaccines hold promise to outperform conventional antigen-based vaccines by virtue of many unique features. However, DNA vaccines have thus far fallen short of expectations, due in part to poor targeting of professional antigen-presenting cells (APC) and low immunogenicity. In this study, we describe a new platform for effective and selective delivery of DNA to APCs in vivo that offers intrinsic immune-enhancing characteristics. This platform is based on conjugation of fifth generation polyamidoamine (G5-PAMAM) dendrimers, a DNA-loading surface, with MHC class II-targeting peptides that can selectively deliver these dendrimers to APCs under conditions that enhance their immune stimulatory potency. DNA conjugated with this platform efficiently transfected murine and human APCs in vitro. Subcutaneous administration of DNA-peptide-dendrimer complexes in vivo preferentially transfected dendritic cells (DC) in the draining lymph nodes, promoted generation of high affinity T cells, and elicited rejection of established tumors. Taken together, our findings show how PAMAM dendrimer complexes can be used for high transfection efficiency and effective targeting of APCs in vivo, conferring properties essential to generate effective DNA vaccines. Cancer Res; 71(24); 7452-62. (C) 2011 AACR.