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Co-transfection Gene Delivery of Dendritic Cells Induced Effective Lymph Node Targeting and Anti-tumor Vaccination

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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 co-transfected 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 CCR7-coding plasmid to induce both the capacity of antigen presentation and lymph node targeting.

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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

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was financially supported by National Natural Science Foundation of China (30973648), NSFC-JSPS joint grant supported by both China and Japan (81011140077), Natural Science Foundation of Zhejiang Province, China (R2090176, LY12H30002) and Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents.

Authors declare have no conflict of interest.

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Authors and Affiliations

  1. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, People’s Republic of China

    Yu-Zhe Chen, Gui-Xin Ruan, Xing-Lei Yao, Li-Ming Li & Jian-Qing Gao

  2. Department of Pharmaceutics, Zhejiang Pharmaceutical College, 888 East section, Yinxian Main Road, The Zone of Higher Education, Ningbo, People’s Republic of China

    Ying Hu

  3. Department of Biomaterials, Field of Tissue Engineering Institute for Frontier Medical Sciences, Kyoto University, 53 Kawanara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan

    Yasuhiko Tabata

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  1. Yu-Zhe Chen
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Correspondence to Jian-Qing Gao.

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Chen, YZ., Ruan, GX., Yao, XL. et al. Co-transfection Gene Delivery of Dendritic Cells Induced Effective Lymph Node Targeting and Anti-tumor Vaccination. Pharm Res 30, 1502–1512 (2013). https://doi.org/10.1007/s11095-013-0985-8

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  • DOI: https://doi.org/10.1007/s11095-013-0985-8

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