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.

PROJECT NARRATIVE Therapeutic outcomes following the dendritic cell (DC)-based vaccination for pancreatic cancer may be limited if an insufficient number of the DC-vaccines reach the draining lymph nodes (LNs). We will use clinically applicable approaches for magnetic DC-vaccine labeling, in which magnetic DC-vaccines can be visualized with advanced MRI methods. Imaging methods will be developed to allow direct, non-invasive, real-time measurements of DC-vaccine homing to draining LNs thus serving as valuable biomarkers for clinical dosimetry as well as the advancement of knowledge and discovery in DC immunotherapy strategies.