Co-transfection gene delivery of dendritic cells induced effective lymph node targeting and anti-tumor vaccination.
OBJECTIVE
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.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058 Zhejiang, People's Republic of China.
Yu-Zhe
YZ
Chen
Gui-Xin
GX
Ruan
Xing-Lei
XL
Yao
Li-Ming
LM
Li
Ying
Y
Hu
Yasuhiko
Y
Tabata
Jian-Qing
JQ
Gao
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D003911:Dextrans / Q000235:genetics / Q000276:immunology; D004705:Endocytosis / Q000235:genetics / Q000276:immunology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7; D013096:Spermine / Q000276:immunology; D014162:Transfection / Q000379:methods; D058951:gp100 Melanoma Antigen / Q000235:genetics / Q000276:immunology
D019496:Cancer Vaccines; C515371:Ccr7 protein, mouse; D003911:Dextrans; D054400:Receptors, CCR7; D058951:gp100 Melanoma Antigen; D013096:Spermine; D004247:DNA