Injectable dendritic cell-carrying alginate gels for immunization and immunotherapy
Injectable dendritic cell-carrying alginate gels for immunization and immunotherapy
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DOI：
10.1016/j.biomaterials.2008.05.033
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发表时间：
2008-09-01
期刊：
影响因子：
14
通讯作者：
Irvine, Darrell J.
中科院分区：
文献类型：
--
作者：
Hori, Yuki;Winans, Amy M.;Irvine, Darrell J.
树突状细胞疫苗，其中负载抗原的树突状细胞（DC）直接注射到患者体内以引发免疫反应，正在开发用于治疗癌症和一些传染病。在这项研究中，我们测试了在可注射水凝胶基质中递送DC的概念，目的是在确定的部位长时间地窝藏树突状细胞，并捕获/浓缩DC分泌的因子，以建立原位炎症环境。为了实现这些目标，开发了藻酸盐的自胶凝制剂，其通过将负载钙的藻酸盐微球与可溶性藻酸盐溶液和树突状细胞混合而获得，该制剂在体内快速胶凝。当在小鼠中皮下注射时，这些含有活化的DC的藻酸盐“疫苗接种节点”在体内一周内将宿主树突状细胞和大量T细胞吸引到注射部位，而一些接种的DC被运输到引流淋巴结。使用过继转移模型来跟踪响应于用抗原负载的DC免疫的T细胞的限定群体，我们表明DC/藻酸盐免疫导致激活的抗原特异性T细胞以依赖于DC的存在的方式募集到藻酸盐基质。因此，这种凝胶/DC免疫系统可能对免疫治疗感兴趣，以在存在由水凝胶基质共同递送的支持因子的情况下引导免疫细胞在实体瘤或感染部位处的积累。(C)2008爱思唯尔有限公司保留所有权利。
Dendritic cell vaccines, in which antigen-loaded dendritic cells (DCs) are injected directly into patients to trigger immune responses, are in development as a treatment for cancer and some infectious diseases. In this study, we tested the concept of delivering DCs in an injectable hydrogel matrix, with the aim of harboring dendritic cells for prolonged time periods at a defined site and trapping/concentrating factors secreted by DCs to establish an inflammatory milieu in situ. To achieve these goals, a self-gelling formulation of alginate was developed, obtained by mixing calcium-loaded alginate microspheres with soluble alginate solution and dendritic cells, a formulation that rapidly gelled in vivo. When injected subcutaneously in mice, these alginate 'vaccination nodes' containing activated DCs attracted both host dendritic cells and a large number of T cells to the injection sites over a week in vivo, while some of the inoculated DCs trafficked to the draining lymph nodes. Using an adoptive transfer model to track a defined population of T cells responding to immunization with antigen-loaded DCs, we show that DC/alginate immunization led to recruitment of activated antigen-specific T cells to the alginate matrix, in a manner dependent on the presence of the DCs. This gel/DC immunization system may thus be of interest for immunotherapy to direct the accumulation of immune cells at solid tumors or infection sites in the presence of supporting factors co-delivered by the hydrogel matrix. (C) 2008 Elsevier Ltd. All rights reserved.