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细胞穿透肽:在疫苗递送中的应用。

Cell-penetrating peptides: application in vaccine delivery.

作者信息

Brooks Nicole A, Pouniotis Dodie S, Tang Choon-Kit, Apostolopoulos Vasso, Pietersz Geoffrey A

机构信息

Bio-Organic and Medicinal Chemistry Laboratory, Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia.

出版信息

Biochim Biophys Acta. 2010 Jan;1805(1):25-34. doi: 10.1016/j.bbcan.2009.09.004. Epub 2009 Sep 25.

Abstract

Recent years have seen a surge in interest in cell-penetrating peptides (CPP) as an efficient means for delivering therapeutic targets into cellular compartments. The cell membrane is impermeable to hydrophilic substances yet linking to CPP can facilitate delivery into cells. Thus the unique translocatory property of CPP ensures they remain an attractive carrier, with the capacity to deliver cargoes in an efficient manner having applications in drug delivery, gene transfer and DNA vaccination. Fundamental for an effective vaccine is the delivery of antigen epitopes to antigen-presenting cells, ensuing processing and presentation and induction of an immune response. Vaccination with proteins or synthetic peptides incorporating CTL epitopes have proven limited due to the failure for exogenous antigens to be presented efficiently to T cells. Linking of antigens to CPP overcomes such obstacles by facilitating cellular uptake, processing and presentation of exogenous antigen for the induction of potent immune responses. This review will encompass the various strategies for the delivery of whole proteins, T cell epitopes and preclinical studies utilizing CPP for cancer vaccines.

摘要

近年来,人们对细胞穿透肽(CPP)作为将治疗靶点递送至细胞区室的有效手段的兴趣激增。细胞膜对亲水性物质是不可渗透的,但与CPP连接可以促进其进入细胞。因此,CPP独特的转运特性确保它们仍然是有吸引力的载体,能够以高效的方式递送货物,在药物递送、基因转移和DNA疫苗接种中具有应用价值。有效疫苗的基础是将抗原表位递送至抗原呈递细胞,随后进行加工、呈递并诱导免疫反应。由于外源抗原无法有效地呈递给T细胞,用包含CTL表位的蛋白质或合成肽进行疫苗接种已被证明存在局限性。将抗原与CPP连接可通过促进细胞摄取、加工和呈递外源抗原来克服这些障碍,从而诱导强烈的免疫反应。本综述将涵盖利用CPP进行癌症疫苗接种时递送完整蛋白质、T细胞表位的各种策略以及临床前研究。

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