| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
University of Iowa Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City
Correspondence: George J. Weiner, Director, University of Iowa Cancer Center, C.E. Block Professor of Cancer Research and Internal Medicine, 5970Z JPP, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242. E-mail: george-weiner{at}uiowa.edu
Over 100 years ago, Coley first explored the use of bacterial products as immunostimulatory therapy for nonbacterial disease. It is now clear that bacterial DNA, and synthetic oligodeoxynucleotides containing specific motifs centered on a CpG dinucleotide (CpG ODN), are potent immunostimulatory agents. The molecular mechanisms responsible for the immunostimulatory effects of CpG ODN have yet to be elucidated fully, although it is clear that CpG ODN act rapidly on a variety of cell types. This includes activation of B cells, natural killer cells, and antigen-presenting cells including monocytes, macrophages, and dendritic cells. These effects have led to evaluation of CpG ODN as immune adjuvants in immunization where they have been shown in animal models to enhance the development of a TH1-type immune response. Preliminary results from clinical trials using CpG ODN as an immune adjuvant are promising. Preclinical studies suggest CpG ODN can also enhance innate immunity against a variety of infections, synergize with monoclonal antibody to enhance antibody-dependent cellular cytotoxicity, and alter the Th1/Th2 balance as a possible treatment for allergic diseases and asthma. Clinical evaluation has recently begun to determine whether promising preclinical results with CpG ODN can be translated into effective and tolerable clinical treatment approaches.
Key Words: B cells • natural killer cells • antigen-presenting cells • allergic diseases • asthma
This article has been cited by other articles:
|
|
 |
|
  G. Oganesyan, S. K. Saha, E. M. Pietras, B. Guo, A. K. Miyahira, B. Zarnegar, and G. Cheng IRF3-dependent Type I Interferon Response in B Cells Regulates CpG-mediated Antibody Production J. Biol. Chem., January 11, 2008; 283(2): 802 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Adamsson, M. Lindblad, A. Lundqvist, D. Kelly, J. Holmgren, and A. M. Harandi Novel immunostimulatory agent based on CpG oligodeoxynucleotide linked to the nontoxic B subunit of cholera toxin. J. Immunol., April 15, 2006; 176(8): 4902 - 4913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Jahrsdorfer, L. Muhlenhoff, S. E. Blackwell, M. Wagner, H. Poeck, E. Hartmann, R. Jox, T. Giese, B. Emmerich, S. Endres, et al. B-Cell Lymphomas Differ in their Responsiveness to CpG Oligodeoxynucleotides Clin. Cancer Res., February 15, 2005; 11(4): 1490 - 1499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Amcheslavsky, W. Zou, and Z. Bar-Shavit Toll-like Receptor 9 Regulates Tumor Necrosis Factor-{alpha} Expression by Different Mechanisms: IMPLICATIONS FOR OSTEOCLASTOGENESIS J. Biol. Chem., December 24, 2004; 279(52): 54039 - 54045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Herbert, J. F. Grosso, M. Dorsey Jr., T. Fu, I. Keydar, M. A. Cejas, D. H. Wreschner, N. Smorodinski, and D. M. Lopez A Unique Mucin Immunoenhancing Peptide with Antitumor Properties Cancer Res., November 1, 2004; 64(21): 8077 - 8084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Stovall, A.-K. Yi, E. A. Meals, A. J. Talati, S. A. Godambe, and B. K. English Role of vav1- and src-related Tyrosine Kinases in Macrophage Activation by CpG DNA J. Biol. Chem., April 2, 2004; 279(14): 13809 - 13816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Lonsdorf, H. Kuekrek, B. V. Stern, B. O. Boehm, P. V. Lehmann, and M. Tary-Lehmann Intratumor CpG-Oligodeoxynucleotide Injection Induces Protective Antitumor T Cell Immunity J. Immunol., October 15, 2003; 171(8): 3941 - 3946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Jian Jun Gao, V. Diesl, T. Wittmann, D. C. Morrison, J. L. Ryan, S. N. Vogel, and M. T. Follettie Bacterial LPS and CpG DNA differentially induce gene expression profiles in mouse macrophages Innate Immunity, August 1, 2003; 9(4): 237 - 243. [Abstract] [PDF]
|
|
|
|
|
|
W. Zou, A. Amcheslavsky, and Z. Bar-Shavit CpG Oligodeoxynucleotides Modulate the Osteoclastogenic Activity of Osteoblasts via Toll-like Receptor 9 J. Biol. Chem., May 2, 2003; 278(19): 16732 - 16740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kerkmann, S. Rothenfusser, V. Hornung, A. Towarowski, M. Wagner, A. Sarris, T. Giese, S. Endres, and G. Hartmann Activation with CpG-A and CpG-B Oligonucleotides Reveals Two Distinct Regulatory Pathways of Type I IFN Synthesis in Human Plasmacytoid Dendritic Cells J. Immunol., May 1, 2003; 170(9): 4465 - 4474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Gao, V. Diesl, T. Wittmann, D. C. Morrison, J. L. Ryan, S. N. Vogel, and M. T. Follettie Regulation of gene expression in mouse macrophages stimulated with bacterial CpG-DNA and lipopolysaccharide J. Leukoc. Biol., December 1, 2002; 72(6): 1234 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. M. Olbrich, S. Schimmer, K. Heeg, K. Schepers, T. N. M. Schumacher, and U. Dittmer Effective Postexposure Treatment of Retrovirus-Induced Disease with Immunostimulatory DNA Containing CpG Motifs J. Virol., October 11, 2002; 76(22): 11397 - 11404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Brown and D. Lillicrap Dangerous liaisons: the role of "danger" signals in the immune response to gene therapy Blood, July 30, 2002; 100(4): 1133 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Campos-Neto, J. R. Webb, K. Greeson, R. N. Coler, Y. A. W. Skeiky, and S. G. Reed Vaccination with Plasmid DNA Encoding TSA/LmSTI1 Leishmanial Fusion Proteins Confers Protection against Leishmania major Infection in Susceptible BALB/c Mice Infect. Immun., June 1, 2002; 70(6): 2828 - 2836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. ZOU, H. SCHWARTZ, S. ENDRES, G. HARTMANN, and Z. BAR-SHAVIT CpG oligonucleotides: novel regulators of osteoclast differentiation FASEB J, March 1, 2002; 16(3): 274 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Decker, S. Hipp, R. J. Kreitman, I. Pastan, C. Peschel, and T. Licht Sensitization of B-cell chronic lymphocytic leukemia cells to recombinant immunotoxin by immunostimulatory phosphorothioate oligodeoxynucleotides Blood, February 15, 2002; 99(4): 1320 - 1326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Billiau and P. Matthys Modes of action of Freund's adjuvants in experimental models of autoimmune diseases J. Leukoc. Biol., December 1, 2001; 70(6): 849 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hafner, R. Zawatzky, C. Hirtreiter, W. A. Buurman, B. Echtenacher, T. Hehlgans, and D. N. Mannel Antimetastatic Effect of CpG DNA Mediated by Type I IFN Cancer Res., July 1, 2001; 61(14): 5523 - 5528. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
