Imaging activated T cells predicts response to cancer vaccines
Imaging activated T cells predicts response to cancer vaccines
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对激活的 T 细胞进行成像可预测对癌症疫苗的反应
DOI：
10.1172/jci98509
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发表时间：
2018-06-01
影响因子：
15.9
通讯作者：
Gambhir, Sanjiv S.
中科院分区：
文献类型：
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作者：
Alam, Israt S.;Mayer, Aaron T.;Gambhir, Sanjiv S.
原位癌症疫苗正处于积极的临床研究中，鉴于其报告的根除局部和播散性恶性肿瘤的能力，认为瘤内疫苗施用激活T细胞介导的免疫应答，其在治疗的肿瘤中开始并全身级联。在这项研究中，我们描述了PET示踪剂Cu-（64-DOTA-AbOX 40），使非侵入性和纵向成像的OX 40，T细胞活化的细胞表面标记。我们报告的时空动态T细胞活化后，在原位接种CpG寡核苷酸在一个双重荷瘤小鼠模型。我们证明，OX 40成像能够预测治疗后第9天的肿瘤反应的基础上，肿瘤示踪剂摄取的第2天，具有更高的准确性比解剖和血液为基础的测量。这些研究提供了局部CpG治疗后整体T细胞活化的关键见解，并表明Cu-64-DOTA-AbOX 40是监测临床癌症免疫治疗策略的有希望的候选者。
In situ cancer vaccines are under active clinical investigation, given their reported ability to eradicate both local and disseminated malignancies, Intratumoral vaccine administration is thought to activate a T cell-mediated immune response, which begins in the treated tumor and cascades systemically. In this study, we describe a PET tracer Cu-(64-DOTA-AbOX40) that enabled noninvasive and longitudinal imaging of OX40, a cell-surface marker of T cell activation. We report the spatiotemporal dynamics of T cell activation following in situ vaccination with CpG oligodeoxynucleotide in a dual tumor-bearing mouse model. We demonstrate that OX40 imaging was able to predict tumor responses on day 9 after treatment on the basis of tumor tracer uptake on day 2, with greater accuracy than both anatomical and blood-based measurements. These studies provide key insights into global T cell activation following local CpG treatment and indicate that Cu-64-DOTA-AbOX40 is a promising candidate for monitoring clinical cancer immunotherapy strategies.