Development of HPF-Labeled DC Vaccines for Treatment and Prognosis of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer mortality in the US with a median survival of 6 months. Surgical resection is currently the only curative treatment but are possible in less than 20% of patients and has a 5-year of only 10%. In recent years, dendritic cell (DC) vaccination has emerged as a novel potential systemic treatment for metastatic PDAC. However, current clinical trials show that DC vaccination is effective in treating only a small subset of patients and has a low efficacy in reducing tumor burden, suggesting that this therapeutic approach needs further optimization. DC vaccine migration to peripheral lymph nodes (LNs) has been shown to predict anti-tumor response and may thus predict therapeutic efficacy as well. Magnetic resonance imaging (MRI), a quantitative real-time non-invasive imaging tool that does not use ionizing radiation, is a well-established method for visualization and characterization of DC migration to LNs. We previously generated DC vaccines labeled with superparamagnetic iron oxide (SPIO) nanoparticles to visualize DC migration in vivo with MRI. However, SPIO is not FDA-approved and cannot be translated for clinical use. In this project, we will use the clinically applicable approach of combining the FDA-approved drugs heparin, protamine, and ferumoxytol to form HPF nanocomplexes for magnetic labeling and visualization of DC vaccines with quantitative MRI methods. These HPF-labeled DCs will be characterized by in vitro assays for DC function, and phantom scans will be performed to quantify the relationship between DC concentration and MR signal. As HPF and its component drugs are all FDA approved, this technique is easily translatable from bench to bedside. Together, we hope to offer insight into the dynamics and kinetics of DC migration in vivo and provide a basis for using imaging to predict therapeutic outcomes in both pre-clinical and clinical research settings.