Malaghan Institute of Medical Research, Wellington, New Zealand.
PLoS One. 2013 May 29;8(5):e65318. doi: 10.1371/journal.pone.0065318. Print 2013.
Cancer immunotherapy with antigen-loaded dendritic cell-based vaccines can induce clinical responses in some patients, but further optimization is required to unlock the full potential of this strategy in the clinic. Optimization is dependent on being able to monitor the cellular events that take place once the dendritic cells have been injected in vivo, and to establish whether antigen-specific immune responses to the tumour have been induced. Here we describe the use of magnetic resonance imaging (MRI) as a simple, non-invasive approach to evaluate vaccine success. By loading the dendritic cells with highly magnetic iron nanoparticles it is possible to assess whether the injected cells drain to the lymph nodes. It is also possible to establish whether an antigen-specific response is initiated by assessing migration of successive rounds of antigen-loaded dendritic cells; in the face of a successfully primed cytotoxic response, the bulk of antigen-loaded cells are eradicated on-route to the node, whereas cells without antigen can reach the node unchecked. It is also possible to verify the induction of a vaccine-induced response by simply monitoring increases in draining lymph node size as a consequence of vaccine-induced lymphocyte trapping, which is an antigen-specific response that becomes more pronounced with repeated vaccination. Overall, these MRI techniques can provide useful early feedback on vaccination strategies, and could also be used in decision making to select responders from non-responders early in therapy.
用负载抗原的树突状细胞疫苗进行癌症免疫疗法可以诱导一些患者产生临床反应，但需要进一步优化，才能在临床上充分发挥这一策略的潜力。优化取决于能否监测到树突状细胞在体内注射后发生的细胞事件，并确定是否诱导了针对肿瘤的抗原特异性免疫反应。在这里，我们描述了使用磁共振成像 (MRI) 作为一种简单、非侵入性的方法来评估疫苗的效果。通过将树突状细胞装载到高磁性的铁纳米粒子上，可以评估注入的细胞是否引流到淋巴结。还可以通过评估连续几轮负载抗原的树突状细胞的迁移来确定是否启动了抗原特异性反应；在成功引发细胞毒性反应的情况下，大量负载抗原的细胞在前往淋巴结的途中被清除，而没有抗原的细胞可以不受阻碍地到达淋巴结。还可以通过监测引流淋巴结大小的增加来简单地验证疫苗诱导的反应的诱导，这是一种由于疫苗诱导的淋巴细胞捕获而引起的抗原特异性反应，随着重复接种，这种反应会变得更加明显。总的来说，这些 MRI 技术可以为疫苗接种策略提供有用的早期反馈，也可以用于在治疗早期从非应答者中选择应答者的决策。
