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

项目摘要 树突状细胞（DC）是一种新兴的、有效的肿瘤免疫治疗形式。然而， 抗原负载的DC（DC疫苗）受其迁移至外周引流淋巴的能力的强烈影响 节点（LN）。因此，关键是监测DC疫苗接种后的体内生物分布， 以优化胰腺癌的DC治疗。在这项研究中，我们提出磁标记DC- 疫苗以允许它们迁移到LN的磁共振成像（MRI）。我们将在临床上 结合FDA批准的药物（ferumoxytol，肝素和鱼精蛋白）用于磁共振成像的适用方法 DC疫苗标记，其中磁性DC疫苗可以用先进的MRI方法可视化。这些 这些技术可能为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。额外的翻译 研究应最终遵循，以评估这些方法的有效性，为早期预测纵向 DC治疗在广泛的肿瘤病因中的结果。 本项目将使用KPC转基因胰腺癌小鼠模型解决以下具体目标。 目的1：优化DC疫苗磁标记的临床应用方法，并确定DC疫苗的免疫原性。 这些疫苗的定量成像特性与体外MRI体模研究;目的2：评估是否 DC疫苗的磁标记允许随后迁移到引流的定量体内MRI 目的3：确定MRI是否监测DC疫苗 迁移到淋巴结可以预测治疗。

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.