Developing MRI-Guided Preventive Dendritic Cell Vaccination Strategy to Avoid Post-surgical Pancreatic Cancer Recurrence and Metastasis

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PROJECT SUMMARY Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer mortality in the US. Surgical resection is the only curative treatment, and due to the high recurrence rate (60%), only 20% survive five years. Chemotherapy and radiotherapy after surgical resection only offer modest improvements in survival. A new approach to prevent tumor recurrence in PDAC patients is urgently needed. We will compare overall survival (OS) after tumor resection between the combination of dendritic cell (DC) vaccination via an improved intraperitoneal, i.p., route, combined with current therapy (gemcitabine), versus the use of preventive DC vaccination alone or gemcitabine alone (Aim 1). Given the relationship between migration to lymph nodes (LNs) and anti-tumor immune response, accurate quantification of DC vaccine migration could serve as an early biomarker for predicting longitudinal response (OS) and elucidating the cause of differential response rates between patients. Understanding factors that affect DC vaccine response rates will enable the titration of vaccine doses to optimize outcomes for individual patients. Thus, we will validate magnetic imaging via quantitative susceptibility mapping (QSM) and ultrashort echo time (UTE) R2* techniques for tracking clinically applicable magnetic-labeled DC vaccines to draining abdominal LNs (Aim 2). We will test whether advanced MRI-tracked DC vaccine homing to LNs can be used as an early imaging biomarker to predict OS of the combination of DC vaccination and gemcitabine treatment post-surgery (Aim 3). The proposed work will meet the significant demand for a novel DC vaccination strategy of cancer therapy that can rapidly be translated to the clinic to prevent relapse after pancreatic tumor surgery while adding an imaging biomarker as a potentially powerful method to simultaneously predict response to the therapy. The success of the proposed preventive DC vaccination strategy and prediction of response to treatment could have a broad impact as a clinical extension to other solid organ systems (e.g., stomach, liver, colorectal, renal, or uterine tumors) as novel adjuvant immunotherapy to prevent relapse after surgery.