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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：
9754617
负责人：
Zhuoli Zhang
金额：
$ 34.22万
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/9754617
关键词：
Address Antigen-Presenting Cells Antigens Biodistribution Biological Markers Biomedical Engineering Cancer Immunology Science Cell Survival Cell physiology Cellular immunotherapy 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 Injections Kinetics Knowledge Discovery Label Lymphoid Tissue Magnetic Resonance Imaging Magnetism Malignant Neoplasms Malignant neoplasm of pancreas Measurement Measures Methods Modeling Monitor Mus ORALIT Operative Surgical Procedures Outcome Pancreatic Ductal Adenocarcinoma Patients Peripheral Pharmaceutical Preparations Physics Prediction of Response to Therapy 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 clinical application clinically relevant dosimetry ferumoxytol image guided imaging biomarker imaging modality imaging properties in vivo in vivo monitoring individual patient insight lymph nodes migration mortality mouse model nanocomplexes novel strategies outcome forecast pancreatic cancer model phantom model pre-clinical research predicting response quantitative imaging temporal measurement therapy outcome translational study tumor uptake vaccine immunotherapy virtual

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.

项目总结