Augmented Anti-tumor Effect of Dendritic Cells Genetically Engineered by Interleukin-12 Plasmid DNA

被引:9
作者
Yoshida, Masataka [1 ]
Jo, Jun-Ichiro [1 ]
Tabata, Yasuhiko [1 ]
机构
[1] Kyoto Univ, Inst Frontier Med Sci, Dept Biomat, Sakyo Ku, Kyoto 6068507, Japan
关键词
Dendritic cells; immune response; anti-tumor effect; cationized dextran; interleukin-12; INTERFERON-GAMMA PRODUCTION; CD4+ T-CELLS; GENE DELIVERY; STEM-CELLS; SPERMINE DERIVATIVES; EXPRESSION PROFILE; CYTOKINE; IL-12; TRAFFICKING; CHEMOKINES;
D O I
10.1163/156856209X434674
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The objective of this study was to genetically engineer dendritic cells (DC) for biological activation and evaluate their anti-tumor activity in a tumor-bearing mouse model. Mouse DC were incubated on the surface of culture dishes which had been coated with the complexes of a cationized dextran and luciferase plasmid DNA complexes plus a cell adhesion protein, Pronectin (R), for gene transfection (reverse transfection). When compared with the conventional transfection where DC were transfected in the medium containing the complexes, the level of gene expression by the reverse method was significantly higher and the time period of gene expression was prolonged. Following the reverse transfection of DC by a plasmid DNA of mouse interleukin-12 (mIL-12) complexed with the cationized dextran, the mIL-12 protein was secreted at higher amounts for a longer time period. When injected intratumorally into mice carrying a mass of B16 tumor cells, the DC genetically activated showed significant anti-tumor activity. (C) Koninklijke Brill NV, Leiden, 2010
引用
收藏
页码:659 / 675
页数:17
相关论文
共 34 条
[2]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[3]   PRODUCTION OF NATURAL-KILLER-CELL STIMULATORY FACTOR (INTERLEUKIN-12) BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS [J].
DANDREA, A ;
RENGARAJU, M ;
VALIANTE, NM ;
CHEHIMI, J ;
KUBIN, M ;
ASTE, M ;
CHAN, SH ;
KOBAYASHI, M ;
YOUNG, D ;
NICKBARG, E ;
CHIZZONITE, R ;
WOLF, SF ;
TRINCHIERI, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (05) :1387-1398
[4]   Cationic liposomes for gene delivery:: From biophysics to biological applications [J].
de Lima, MCP ;
Neves, S ;
Filipe, A ;
Düzgünes, N ;
Simoes, S .
CURRENT MEDICINAL CHEMISTRY, 2003, 10 (14) :1221-1231
[5]   Cationic polymer based gene delivery systems [J].
De Smedt, SC ;
Demeester, J ;
Hennink, WE .
PHARMACEUTICAL RESEARCH, 2000, 17 (02) :113-126
[6]   Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines [J].
Dieu-Nosjean, MC ;
Vicari, A ;
Lebecque, S ;
Caux, C .
JOURNAL OF LEUKOCYTE BIOLOGY, 1999, 66 (02) :252-262
[7]   Cationic lipid-DNA complexes for gene therapy: Understanding the relationship between complex structure and gene delivery pathways at the molecular level [J].
Ewert, K ;
Slack, NL ;
Ahmad, A ;
Evans, HM ;
Lin, AJ ;
Samuel, CE ;
Safinya, CR .
CURRENT MEDICINAL CHEMISTRY, 2004, 11 (02) :133-149
[8]   Cellular and molecular mechanisms underlying IL-12-induced tumor regression [J].
Fujiwara, H ;
Clark, SC ;
Hamaoka, T .
INERLEUKIN 12: CELLULAR AND MOLECULAR IMMUNOLOGY OF AN IMPORTANT REGULATORY CYTOKINE, 1996, 795 :294-309
[9]   DC-based cancer vaccines [J].
Gilboa, Eli .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (05) :1195-1203
[10]   IL-12 acts directly on DC to promote nuclear localization of NF-κB and primes DC for IL-12 production [J].
Grohmann, U ;
Belladonna, ML ;
Bianchi, R ;
Orabona, C ;
Ayroldi, E ;
Fioretti, MC ;
Puccetti, P .
IMMUNITY, 1998, 9 (03) :315-323