Efficient nonviral transfection of dendritic cells and their use for in vivo immunization

被引:79
作者
Irvine, AS
Trinder, PKE
Laughton, DL
Ketteringham, H
McDermott, RH
Reid, SCH
Haines, AMR
Amir, A
Husain, R
Doshi, R
Young, LS
Mountain, A
机构
[1] Univ Keele, Keele ST5 5SP, Staffs, England
[2] Univ Birmingham, CRC, Inst Canc Studies, Birmingham B15 2TA, W Midlands, England
关键词
nonviral transfection; dendritic cells; cancer immunotherapy; genetic modification;
D O I
10.1038/82383
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Immunization with dendritic cells (DCs) transfected with genes encoding tumor-associated antigens (TAAs) is a highly promising approach to cancer immunotherapy. We have developed a system, using complexes of plasmid DNA expression constructs with the cationic peptide CL22, that transfects human monocyte-derived DCs much more efficiently than alternative nonviral agents, After CL22 transfection, DCs expressing antigens stimulated autologous T cells in vitro and elicited primary immune responses in syngeneic mice, in an antigen-specific manner. Injection of CL22-transfected DCs expressing a TAA, but not DCs pulsed with a TAA-derived peptide, protected mice from lethal challenge with tumor cells in an aggressive model of melanoma, The CL22 system is a fast and efficient alternative to viral vectors for engineering DCs for use in immunotherapy and research.
引用
收藏
页码:1273 / 1278
页数:6
相关论文
共 31 条
[1]  
Arthur JF, 1997, CANCER GENE THER, V4, P17
[2]   Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma [J].
Bloom, MB ;
PerryLalley, D ;
Robbins, PF ;
Li, Y ;
ElGamil, M ;
Rosenberg, SA ;
Yang, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (03) :453-459
[3]   MOLECULAR CHARACTERIZATION OF A HUMAN TYROSINASE-RELATED-PROTEIN-2 CDNA - PATTERNS OF EXPRESSION IN MELANOCYTIC CELLS [J].
BOUCHARD, B ;
DELMARMOL, V ;
JACKSON, IJ ;
CHERIF, D ;
DUBERTRET, L .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1994, 219 (1-2) :127-134
[4]  
CORICO R, 2000, CURRENT PROTOCOLS IM
[5]  
De Veerman M, 1999, J IMMUNOL, V162, P144
[6]  
DIBRINO M, 1993, J IMMUNOL, V151, P5930
[7]   Nomenclature for synthetic gene delivery systems [J].
Felgner, PL ;
Barenholz, Y ;
Behr, JP ;
Cheng, SH ;
Cullis, P ;
Huang, L ;
Jessee, JA ;
Seymour, L ;
Szoka, F ;
Thierry, AR ;
Wagner, E ;
Wu, G .
HUMAN GENE THERAPY, 1997, 8 (05) :511-512
[8]   Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells [J].
Hsu, FJ ;
Benike, C ;
Fagnoni, F ;
Liles, TM ;
Czerwinski, D ;
Taidi, B ;
Engleman, EG ;
Levy, R .
NATURE MEDICINE, 1996, 2 (01) :52-58
[9]   The central role of CD4+ T cells in the antitumor immune response [J].
Hung, K ;
Hayashi, R ;
Lafond-Walker, A ;
Lowenstein, C ;
Pardoll, D ;
Levitsky, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (12) :2357-2368
[10]   Efficient transduction of mature CD83+ dendritic cells using recombinant adenovirus suppressed T cell stimulatory capacity [J].
Jonuleit, H ;
Tüting, T ;
Steitz, J ;
Brück, J ;
Giesecke, A ;
Steinbrink, K ;
Knop, J ;
Enk, AH .
GENE THERAPY, 2000, 7 (03) :249-254