Co-transfection Gene Delivery of Dendritic Cells Induced Effective Lymph Node Targeting and Anti-tumor Vaccination
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RESEARCH PAPER
Co-transfection Gene Delivery of Dendritic Cells Induced Effective Lymph Node Targeting and Anti-tumor Vaccination Yu-Zhe Chen & Gui-Xin Ruan & Xing-Lei Yao & Li-Ming Li & Ying Hu & Yasuhiko Tabata & Jian-Qing Gao Received: 11 October 2012 / Accepted: 9 January 2013 # Springer Science+Business Media New York 2013
ABSTRACT Purpose Successful genetically engineered Dendritic Cell (DC) can enhance DC’s antigen presentation and lymph node migration. The present study aims to genetically engineer a DC using an efficient non-viral gene delivery vector to induce a highly efficient antigen presentation and lymph node targeting in vivo. Methods Spermine-dextran (SD), a cationic polysaccharide vector, was used to prepare a gene delivery system for DC engineering. Transfection efficiency, nuclear trafficking, and safety of the SD/DNA complex were evaluated. A vaccine prepared by engineering DC with SD/gp100, a plasmid encoding melanoma-associated antigen, was injected subcutaneously into mice to evaluate the tumor suppression. The migration of the engineered DCs was also evaluated in vitro and in vivo. Results SD/DNA complex has a better transfection behavior in vitro than commercially purchased reagents. The DC vaccine cotransfected with plasmid coding CCR7, a chemokine receptor essential for DC migration, and plasmid coding gp100 displayed superior tumor suppression than that with plasmid coding gp100 alone. Migration assay demonstrated that DC transfected with SD/CCR7 can promote DC migration capacity. Conclusions The study is the first to report the application of nonviral vector SD to co-transfect DC with gp100 and CCR7coding plasmid to induce both the capacity of antigen presentation and lymph node targeting. Y.-Z. Chen : G.-X. Ruan : X.-L. Yao : L.-M. Li : J.-Q. Gao (*) Institute of Pharmaceutics, College of Pharmaceutical Sciences Zhejiang University, 866 Yuhangtang Road Hangzhou 310058 Zhejiang, People’s Republic of China e-mail: [email protected] Y. Hu Department of Pharmaceutics Zhejiang Pharmaceutical College 888 East section, Yinxian Main Road, The Zone of Higher Education Ningbo, People’s Republic of China Y. Tabata Department of Biomaterials, Field of Tissue Engineering Institute for Frontier Medical Sciences, Kyoto University 53 Kawanara-cho, Shogoin, Sakyo-ku 606-8507, Kyoto, Japan
KEY WORDS CCR7 . dendritic cell . gene delivery . immunotherapy . spermine-dextran ABBREVIATIONS APC antigen presenting cell CCL21 C-C Chemokine ligand 21 CCR7 C-C chemokine receptor type7 CLSM confocal laser scanning microscopy DC dendritic cell EGFP enhanced green fluorescent protein FITC fluorescein isothiocyanate GM-CSF granulocyte-macrophage colony stimulating factor MHC major histocompatibility complex MβCD methyl-β-cyclodextrin PI propidium iodide SD spermine-dextran TAA tumor associated antigen
INTRODUCTION Cancer is one of the leading causes of death worldwide (1), and immunotherapy is expected to be a promising approach to conquer this disease. Recent findings suggest that antitumor vaccines
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