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Optimal therapeutic strategy using antigen‐containing liposomes selectively delivered to antigen‐presenting cells

机译:使用选择性地递送至抗原呈递细胞的含抗原脂质体的最佳治疗策略

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摘要

Recent immunotherapies have shown clinical success. In particular, vaccines based on particulate antigen (Ag) are expected to be implemented based on their efficacy. In the current study, we describe a strategy entailing Ag‐encapsulating PEG‐modified liposomes (PGL‐Ag) as antigen protein delivery devices and show that the success of the liposome depends on the antigen‐presenting cell (APC) capacity; after administration of PGL‐Ag, dendritic cells (DCs) in particular take up the Ag and subsequently prime T cells. For the generation of antitumor T cell responses in the lymphoid tissues, the function of encapsulated Ag‐capturing DCs in vivo could be a biomarker. We next designed a prime‐boost strategy to enhance the antitumor effects of the PGL‐Ag. In the tumor sites, we show that Ag retention in nanoparticle‐capturing DCs promotes a robust antitumor response. Thus, this efficient particulate Ag‐based host antigen‐presenting cell delivery strategy provides a bridge between innate and adaptive immune response and offers a novel therapeutic option against tumor cells.
机译:最近的免疫疗法已显示出临床成功。特别地,基于它们的功效,预期将基于颗粒抗原(Ag)的疫苗被实施。在当前的研究中,我们描述了一种策略,该方法将用Ag包囊的PEG修饰的脂质体(PGL-Ag)作为抗原蛋白递送装置,并表明脂质体的成功取决于抗原呈递细胞(APC)的能力。施用PGL-Ag后,树突状细胞(DC)特别吸收Ag,随后吸收初生T细胞。为了在淋巴组织中产生抗肿瘤T细胞反应,体内包裹Ag捕获的DC的功能可能是生物标记。接下来,我们设计了一种加强免疫的策略来增强PGL-Ag的抗肿瘤作用。在肿瘤部位,我们显示Ag保留在捕获纳米颗粒的DC中会促进强大的抗肿瘤反应。因此,这种有效的基于Ag的颗粒状宿主抗原呈递细胞递送策略为先天性和适应性免疫应答之间架起了桥梁,并提供了针对肿瘤细胞的新型治疗选择。

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