Magnetovaccination as a novel method to assess and quantify dendritic cell tumor antigen capture and delivery to lymph nodes.
Magnetovaccination as a novel method to assess and quantify dendritic cell tumor antigen capture and delivery to lymph nodes.
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DOI：
10.1158/0008-5472.can-08-3691
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发表时间：
2009-04-01
期刊：
影响因子：
11.2
通讯作者：
Levitsky HI
中科院分区：
文献类型：
--
作者：
Long CM;van Laarhoven HW;Bulte JW;Levitsky HI
限制疫苗免疫反应的一个主要参数是激活的抗原提呈细胞(APC)的数量，这些细胞捕获抗原并迁移到引流淋巴结(LN)。目前，缺乏一种定量的、非侵入性的监测体内抗原捕获和传递的技术。使用细胞磁共振成像(MRI)是一种很有前途的方法；然而，细胞成像目前需要在体外用造影剂预先标记细胞，然后将细胞重新引入被监测对象。在此，我们描述了一种体内标记方法，该方法依赖于超顺磁性氧化铁(SPIO)从肿瘤细胞到细胞内的原位转移，以在肿瘤疫苗模型中定量APC向LNS的输送。以肿瘤细胞为基础的疫苗免疫小鼠，该疫苗经过照射并用SPIO标记。捕获SPIO的APC随着时间的推移被成像，因为它们在LNS中积累。我们在这里展示了MRI能够在体内监测磁性标记的APC的运输诱导肿瘤特异性免疫反应，并且这些细胞可以在体外被磁性恢复。体内和体外APC的定量之间有很好的相关性，分辨率足以检测到佐剂引起的APC转运增加。这项研究展示了磁疫苗接种和MRI细胞跟踪的潜力，通过基于MRI的无创性APC数量的量化，系统地评估了与疫苗治疗优化相关的关键参数。
A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of super-paramagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell–based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers.