Therapeutic potential of Toll-like receptor 9 activation

被引：1035
作者：
Krieg, Arthur M. [1 ]
机构：
[1] Coley Pharmaceut Grp Inc, Wellesley, MA 02481 USA
来源：
NATURE REVIEWS DRUG DISCOVERY | 2006年 / 5卷 / 06期
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
[81]   CpG oligodeoxynucleotides enhance host defense during murine tuberculosis [J].
Juffermans, NP ;
Leemans, JC ;
Florquin, S ;
Verbon, A ;
Kolk, AH ;
Speelman, P ;
van Deventer, SJH ;
van der Poll, T .
INFECTION AND IMMUNITY, 2002, 70 (01) :147-152
[82]   Distinct response of human B cell subpopulations in recognition of an innate immune signal, CpG DNA [J].
Jung, J ;
Yi, AK ;
Zhang, X ;
Choe, J ;
Li, L ;
Choi, YS .
JOURNAL OF IMMUNOLOGY, 2002, 169 (05) :2368-2373
[83]  
Jurk M., 2005, CLIN INVEST MED, V27, P2333
[84]   Toll-like receptor 9: modulation of recognition and cytokine induction by novel synthetic CpG DNAs [J].
Kandimalla, ER ;
Zhu, FG ;
Bhagat, L ;
Yu, D ;
Agrawal, S .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2003, 31 :654-658
[85]   Toll-like receptor 9-induced type IIFN protects mice from experimental colitis [J].
Katakura, K ;
Lee, J ;
Rachmilewitz, D ;
Li, G ;
Eckmann, L ;
Raz, E .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (03) :695-702
[86]   Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6 [J].
Kawai, T ;
Sato, S ;
Ishii, KJ ;
Coban, C ;
Hemmi, H ;
Yamamoto, M ;
Terai, K ;
Matsuda, M ;
Inoue, J ;
Uematsu, S ;
Takeuchi, O ;
Akira, S .
NATURE IMMUNOLOGY, 2004, 5 (10) :1061-1068
[87]   Plasmacytoid dendritic cell-derived IFN-α induces TNF-related apoptosis-inducing ligand/Apo-2L-mediated antitumor activity by human monocytes following CpG oligodeoxynucleotide stimulation [J].
Kemp, TJ ;
Elzey, BD ;
Griffith, TS .
JOURNAL OF IMMUNOLOGY, 2003, 171 (01) :212-218
[88]   Spontaneous formation of nucleic acid-based nanoparticles is responsible for high interferon-α induction by CpG-A in plasmacytoid dendritic cells [J].
Kerkmann, M ;
Costa, LT ;
Richter, C ;
Rothenfusser, S ;
Battiany, J ;
Hornung, V ;
Johnson, J ;
Englert, S ;
Ketterer, T ;
Heckl, W ;
Thalhammer, S ;
Endres, S ;
Hartmann, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (09) :8086-8093
[89]   Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1-KLH and GD3-KLH conjugates [J].
Kim, SK ;
Ragupathi, G ;
Cappello, S ;
Kagan, E ;
Livingston, PO .
VACCINE, 2000, 19 (4-5) :530-537
[90]  
Kline JN, 1998, J IMMUNOL, V160, P2555
45678910111213