The immunobiology and clinical potential of immunostimulatory CpG oligodeoxynucleotides.
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.
Weiner
G J
GJ
University of Iowa Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City 52242, USA. george-weiner@uiowa.edu
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy; D002986:Clinical Trials as Topic; D018899:CpG Islands; D004269:DNA, Bacterial / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D007114:Immunization; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000188:drug therapy; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D017382:Reactive Oxygen Species; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D018927:Anti-Asthmatic Agents; C408982:CPG-oligonucleotide; D004269:DNA, Bacterial; D008222:Lymphokines; D009838:Oligodeoxyribonucleotides; D017382:Reactive Oxygen Species