In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles
In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles
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DOI：
10.1073/pnas.0509541102
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发表时间：
2005-12-20
影响因子：
11.1
通讯作者：
Fréchet, JMJ
中科院分区：
文献类型：
--
作者：
Kwon, YJ;James, E;Fréchet, JMJ
激活免疫系统以触发特定反应是疫苗开发中的一大挑战。特别是，激活足够的细胞毒性T淋巴细胞介导的细胞免疫，这对治疗包括癌症和艾滋病在内的许多疾病至关重要，已被证明是特别具有挑战性的。在这项研究中，抗原被包裹在可酸降解的聚合物颗粒载体中，以级联细胞毒性T淋巴细胞的激活。为了靶向树突状细胞，最强大的抗原提呈细胞，即颗粒载体，进一步与单抗偶联。一系列体外和体内研究表明，受体介导的树突状细胞对抗体结合颗粒的摄取增加，携带颗粒的树突状细胞向淋巴结迁移，刺激幼稚T细胞，导致细胞免疫反应增强，这一点被特异性细胞溶解和干扰素-γ分泌所证实。
Activating the immune system to trigger a specific response is a major challenge in vaccine development. In particular, activating sufficient cytotoxic T lymphocyte-mediated cellular immunity, which is crucial for the treatment of many diseases including cancer and AIDS, has proven to be especially challenging. In this study, antigens were encapsulated in acid-degradable polymeric particle carriers to cascade cytotoxic T lymphocyte activation. To target dendritic cells, the most potent antigen-presenting cells, the particle carriers, were further conjugated with monoclonal antibodies. A series of ex vivo and in vivo studies have shown increased receptor-mediated uptake of anti body-conjugated particles by dendritic cells as well as migration of particle-carrying dendritic cells to lymph nodes and stimulation of naive T cells leading to enhanced cellular immune response as confirmed by specific cell lysis and IFN-gamma secretion.