From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA.
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.
Krieg
A M
AM
Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA. akrieg@coleypharma.com
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000628:therapy; D015551:Autoimmunity / Q000187:drug effects; D018899:CpG Islands; D004269:DNA, Bacterial / Q000235:genetics*; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy; D007113:Immunity, Innate / Q000187:drug effects; D007167:Immunotherapy; D009369:Neoplasms / Q000628:therapy; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D004269:DNA, Bacterial; D020319:Oligodeoxyribonucleotides, Antisense