From bugs to drugs: Therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA

被引:51
作者
Krieg, AM
机构
[1] Coley Pharmaceut Grp, Wellesley, MA 02481 USA
[2] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA
[3] Dept Vet Affairs Med Ctr, Iowa City, IA 52246 USA
来源
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT | 2001年 / 11卷 / 03期
关键词
D O I
10.1089/108729001300338717
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several types of immune cells possess pattern recognition receptors (PRR) that can distinguish prokaryotic DNA from vertebrate DNA by detecting unmethylated CpG dinucleotides in particular base contexts (CpG motifs), Bacterial DNA or synthetic oligodeoxynucleotides containing these CpG motifs activate both innate and acquired immune responses that have evolved to protect against intracellular infections, These T helper 1 (Th1)-like immune responses include activation of B cells, dendritic cells, macrophages, and natural killer (NK) cells. CpG DNA-induced immune activation can protect against infection either alone or in combination with a vaccine and is effective in the immunotherapy of allergic diseases and cancer. Human clinical trials using such CpG DNA are currently underway.
引用
收藏
页码:181 / 188
页数:8
相关论文
共 99 条
[31]  
Iho S, 1999, J IMMUNOL, V163, P3642
[32]  
Jakob T, 1998, J IMMUNOL, V161, P3042
[33]   Synthetic oligodeoxynucleotides containing CpG motifs enhance immunogenicity of a peptide malaria vaccine in Aotus monkeys [J].
Jones, TR ;
Obaldia, N ;
Gramzinski, RA ;
Charoenvit, Y ;
Kolodny, N ;
Kitov, S ;
Davis, HL ;
Krieg, AM ;
Hoffman, SL .
VACCINE, 1999, 17 (23-24) :3065-3071
[34]   BINDING OF OLIGOGUANYLATE TO SCAVENGER RECEPTORS IS REQUIRED FOR OLIGONUCLEOTIDES TO AUGMENT NK CELL-ACTIVITY AND INDUCE IFN [J].
KIMURA, Y ;
SONEHARA, K ;
KURAMOTO, E ;
MAKINO, T ;
YAMAMOTO, S ;
YAMAMOTO, T ;
KATAOKA, T ;
TOKUNAGA, T .
JOURNAL OF BIOCHEMISTRY, 1994, 116 (05) :991-994
[35]   CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma [J].
Kline, JN ;
Krieg, AM ;
Waldschmidt, TJ ;
Ballas, ZK ;
Jain, V ;
Businga, TR .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1999, 104 (06) :1258-1264
[36]  
Kline JN, 1998, J IMMUNOL, V160, P2555
[37]  
Kline JN, 2000, CURR TOP MICROBIOL, V247, P211
[38]   CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma [J].
Klinman, DM ;
Yi, AK ;
Beaucage, SL ;
Conover, J ;
Krieg, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :2879-2883
[39]  
Kovarik J, 1999, J IMMUNOL, V162, P1611
[40]  
Krieg A M, 1991, Antisense Res Dev, V1, P161