Therapeutic potential of Toll-like receptor 9 activation

被引:1017
作者
Krieg, Arthur M. [1 ]
机构
[1] Coley Pharmaceut Grp Inc, Wellesley, MA 02481 USA
关键词
D O I
10.1038/nrd2059
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
In the decade since the discovery that mouse B cells respond to certain unmethylated CpG dinucleotides in bacterial DNA, a specific receptor for these 'CpG motifs' has been identified, Toll-like receptor 9 (TLR9), and a new approach to immunotherapy has moved into the clinic based on the use of synthetic oligodeoxynucleotides (ODN) as TLR9 agonists. This review highlights the current understanding of the mechanism of action of these CpG ODN, and provides an overview of the preclinical data and early human clinical trial results using these drugs to improve vaccines and treat cancer, infectious disease and allergy/asthma.
引用
收藏
页码:471 / 484
页数:14
相关论文
共 210 条
  • [111] A review of issues in the pharmacokinetics and toxicology of phosphorothioate antisense oligonucleotides
    Levin, AA
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1999, 1489 (01): : 69 - 84
  • [112] CpG DNA-mediated immune response in pulmonary endothelial cells
    Li, J
    Ma, Z
    Tang, ZL
    Stevens, T
    Pitt, B
    Li, S
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2004, 287 (03) : L552 - L558
  • [113] CpG DNA redirects class-switching towards "Th1-like" Ig isotype production via TLR9 and MyD88
    Lin, L
    Gerth, AJ
    Peng, SL
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (05) : 1483 - 1487
  • [114] LINK B, IN PRESS J IMMUNOTHE
  • [115] CpG-DNA-mediated transient lymphadenopathy is associated with a state of Th1 predisposition to antigen-driven responses
    Lipford, GB
    Sparwasser, T
    Zimmermann, S
    Heeg, K
    Wagner, H
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (03) : 1228 - 1235
  • [116] CpG-containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen: a new class of vaccine adjuvants
    Lipford, GB
    Bauer, M
    Blank, C
    Reiter, R
    Wagner, H
    Heeg, K
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (09) : 2340 - 2344
  • [117] CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells
    Liu, NS
    Ohnishi, N
    Ni, L
    Akira, SZ
    Bacon, KB
    [J]. NATURE IMMUNOLOGY, 2003, 4 (07) : 687 - 693
  • [118] IPC: Professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors
    Liu, YJ
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2005, 23 : 275 - 306
  • [119] The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells
    Lugo-Villarino, G
    Ito, S
    Klinman, DM
    Glimcher, LH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (37) : 13248 - 13253
  • [120] Maletto B, 2002, J LEUKOCYTE BIOL, V72, P447