414e Co-Delivery of Cationic Polymers and Adenovirus Enhance Tumor Protection In a Murine Model of Prostate Cancer

Jessica B. Graham, Department of Chemical Engineering, University of Iowa, 115 S Grand Avenue, 201 PHAR, Iowa City, IA 52242, Elisabeth Donahey, Division of Pharmacy, University of Iowa, 201 Pharmacy Building, 115 S Grand Avenue, Iowa City, IA 52242, David M. Lubaroff, Department of Urology; Holden Comprehensive Cancer Center, University of Iowa, 375 Newton Road, 3210 MERF, Iowa City, IA 52242, and Aliasger K. Salem, Department of Chemical Engineering, Division of Pharmaceutics, Holden Comprehensive Cancer Center, University of Iowa, 115 S Grand Avenue, S228 PHAR, Iowa City, IA 52242.

Prostate cancer is the most common non-skin cancer in America, and the most commonly diagnosed cancer among males. When metastatic, the disease is ultimately incurable. Consequently, alternative strategies to current treatments are sought, especially in the area of immunotherapy. Vaccine immunotherapy using a specific antigen can be used to stimulate the body's immune response for targeted destruction of cancer cells and for prevention of tumor recurrence. Adenovirus-based vaccines have been successful in inducing an immune response to certain cancers and limiting tumor growth. To enhance this anti-tumor activity, we propose the combination of a viral system with a non-viral system, in the form of the cationic polymer poly ethylenimine (PEI). PEI complexes with DNA to form nanoparticles that can be used in gene delivery. We show that PEI can upregulate the CD80 and CD86 markers of maturation and activation in dendritic cells, a process necessary for launching a robust antigen-specific immune response in the body. We also show that PEI complexed with an antigen-specific adenovirus provides increased tumor protection in a murine tumor model.