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

MRI 引导的基于树突状细胞的胰腺癌疫苗免疫治疗

基本信息

批准号：
9184977
负责人：
Zhuoli Zhang
金额：
$ 34.94万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9184977
关键词：
Address Antigen-Presenting Cells Antigens Biodistribution Biological Markers Biomedical Engineering Cancer Immunology Science Cell Survival Cell physiology Clinical Clinical Research Clinical Trials Contrast Media Cytotoxic T-Lymphocytes Dendritic Cell Therapy Dendritic Cell Vaccine Dendritic Cells Detection Disease Dose Etiology Excision FDA approved Future Genetic Goals Heparin Histologic Homing Human Imagery Imaging Phantoms Immunotherapy In Vitro Injection of therapeutic agent Kinetics Knowledge Discovery Label Lymphoid Tissue Magnetic Resonance Imaging Magnetism Malignant Neoplasms Malignant neoplasm of pancreas Measurement Measures Methods Modeling Monitor Mus Operative Surgical Procedures Outcome Pancreatic Ductal Adenocarcinoma Patients Peripheral Pharmaceutical Preparations Physics Property Protamines Protocols documentation Radiology Specialty Relaxation Site Techniques Time Transgenic Mice Transgenic Organisms Treatment Efficacy Treatment outcome Tumor Antigens Vaccination Vaccines base cancer immunotherapy cancer therapy cell motility chemotherapy clinically relevant dosimetry ferumoxytol image guided imaging biomarker imaging modality in vivo individual patient insight lymph nodes migration mortality mouse model novel strategies outcome forecast phantom model pre-clinical predicting response quantitative imaging temporal measurement therapy outcome translational study treatment response tumor uptake

项目摘要

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.

项目摘要树突状细胞（DC）是一种新出现的癌症免疫治疗形式。但是，抗原负载的DC（DC-vaccines）受到其迁移到外周排水淋巴的能力的强烈影响节点（LNS）。因此，在疫苗接种后，监测DC-VACCINE的体内生物分布至关重要为了优化胰腺癌的直流治疗。在这项研究中，我们提出了磁性标记DC- 疫苗允许其迁移到LN的磁共振成像（MRI）。我们将在临床上使用适用的方法结合了FDA批准的药物（铁氧基二醇，肝素和精神素） DC-疫苗的标记，其中磁性DC-VACCINE可以使用高级MRI方法可视化。这些技术可能会提供对体内DC迁移的动力学和动力学的未来见解对临床前和临床研究环境中的治疗结果的影响。其他翻译研究最终应遵循以评估这些方法的效力，以便早期预测纵向 DC治疗期间的结局在广泛的肿瘤病因中。该项目将使用胰腺癌的KPC转基因小鼠模型来解决以下特定目标。目的1：优化用于临床适用的DC-VACCINE磁性标记的方法，并确定通过体外MRI幻影研究，这些疫苗的定量成像特性；目标2：评估是否 DC疫苗的磁标记允许随后迁移到排水的体内MRI定量MRI 基于DC的疫苗接种后的LN；目标3：确定该MRI是否监视DC-VACCINE 迁移到LN可以预测治疗。