MRI-Guided Dendritic-Cell-Based Vaccine Immunotherapy for Pancreatic Cancer

项目总结 树突状细胞(DC)是一种新兴的、有效的肿瘤免疫治疗方法。然而，这种药物的功效 抗原负载的树突状细胞(DC疫苗)受其向外周引流淋巴迁移能力的强烈影响 节点(LN)。因此，监测DC疫苗接种后在体内的生物分布是至关重要的。 目的：优化胰腺癌DC治疗方案。在这项研究中，我们提出了磁性标记DC- 疫苗使其能够通过磁共振成像(MRI)检测其向LNS的迁移。我们将在临床上使用 联合FDA批准的药物(阿魏酸甘油、肝素和鱼精蛋白)治疗磁疗的适用方法 DC疫苗标记，其中磁性DC疫苗可以用先进的MRI方法进行可视化。这些 这些技术可能会提供对DC在体内迁移的动力学和动力学以及相关的 在临床前和临床研究环境中对治疗结果的影响。其他翻译版本 最终应该进行研究，以评估这些方法对早期预测纵向癌症的有效性。 DC治疗在多种肿瘤病因中的结果。 本项目将使用KPC转基因小鼠胰腺癌模型来解决以下具体目标。 目的1：优化临床适用的DC疫苗磁性标记方法，并确定 用体外磁共振成像模型研究这些疫苗的定量成像特性；目标2：评估 DC疫苗的磁性标记使随后的迁移到引流的体内MRI得以定量 目标3：确定MRI是否监测DC疫苗 移行到LNS可以预测治疗情况。

PROJECT SUMMARY Dendritic Cell (DC) is a newly emerging and potent form of cancer immune therapy. However, the efficacy of antigen-loaded DCs (DC-vaccines) is strongly influenced by their ability to migrate to peripheral draining lymph nodes (LNs). Therefore, it is critical to monitor the in vivo biodistribution of DC-vaccines after vaccination in order to optimize DC therapy for pancreatic cancer. In this study, we propose magnetically labeling DC- vaccines to permit magnetic resonance imaging (MRI) of their migration to LNs. We will use clinically applicable approaches combining FDA-approved drugs (ferumoxytol, heparin, and protamine) for magnetic DC-vaccine labeling, in which magnetic DC-vaccines can be visualized with advanced MRI methods. These techniques may offer future insights into the dynamics and kinetics of DC migration in vivo and the related impacts upon therapeutic outcomes in both pre-clinical and clinical research settings. Additional translational studies should ultimately follow to evaluate the efficacy of these approaches for early prediction of longitudinal outcomes during DC therapy in a broad range of tumor etiologies. This project will address the following Specific Aims using KPC transgenic mouse model of pancreatic cancer. Aim 1: To optimize clinically applicable methods for magnetic-labeling of DC-vaccines and determine the quantitative imaging properties of these vaccines with in vitro MRI phantom studies; Aim 2: To assess whether magnetic-labeling of the DC-vaccine permits quantitative in vivo MRI of subsequent migration to the draining LNs following DC-based vaccination; and Aim 3: To determine whether that MRI monitored DC-vaccine migration to LNs can predict therapy.