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.
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.
Authors: N Okada; N Mori; R Koretomo; Y Okada; T Nakayama; O Yoshie; H Mizuguchi; T Hayakawa; S Nakagawa; T Mayumi; T Fujita; A Yamamoto Journal: Gene Ther Date: 2005-01 Impact factor: 5.250
Authors: A Rughetti; M Biffoni; M Sabbatucci; H Rahimi; I Pellicciotta; A Fattorossi; L Pierelli; G Scambia; M Lavitrano; L Frati; M Nuti Journal: Gene Ther Date: 2000-09 Impact factor: 5.250
Authors: Richard K Yang; Nicholas A Kalogriopoulos; Alexander L Rakhmilevich; Erik A Ranheim; Songwon Seo; Kyungmann Kim; Kory L Alderson; Jacek Gan; Ralph A Reisfeld; Stephen D Gillies; Jacquelyn A Hank; Paul M Sondel Journal: J Immunol Date: 2012-07-27 Impact factor: 5.422
Authors: N Okada; Y Masunaga; Y Okada; H Mizuguchi; S Iiyama; N Mori; A Sasaki; S Nakagawa; T Mayumi; T Hayakawa; T Fujita; A Yamamoto Journal: Gene Ther Date: 2003-10 Impact factor: 5.250
Authors: P G Coulie; V Brichard; A Van Pel; T Wölfel; J Schneider; C Traversari; S Mattei; E De Plaen; C Lurquin; J P Szikora; J C Renauld; T Boon Journal: J Exp Med Date: 1994-07-01 Impact factor: 14.307