Recent advances in the development of immunostimulatory oligonucleotides.
Some immune cells recognize distinct molecular structures present in pathogens through specific pattern recognition receptors that are able to distinguish prokaryotic DNA from vertebrate DNA. The detection of invading microbial DNA is based on the recognition of unmethylated deoxycytidyl-deoxyguanosin dinucleotide (CpG) motifs. Synthetic oligonucleotides (ODNs) containing these CpG motifs are able to activate both innate and acquired immune responses through a signaling pathway involving Toll-like receptor 9 (TLR9). Depending on the sequence, length, as well as number and positions of CpG motifs in an ODN, distinct immunostimulatory profiles can be observed. These immunostimulatory profiles can be further modified and fine-tuned by appropriate chemical modifications, leading to preclinical and clinical development of CpG ODNs in cancer, allergy, asthma and infectious diseases.
Uhlmann
Eugen
E
Coley Pharmaceutical GmbH, Elisabeth-Selbert-Strasse 9, D-40764 Langenfeld, Germany. euhlmann@coleypharma.com
Vollmer
Joerg
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018899:CpG Islands / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007239:Infections / Q000188:drug therapy; D009841:Oligonucleotides / Q000494:pharmacology* / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051217:Toll-Like Receptor 9
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D006571:Heterocyclic Compounds; D009841:Oligonucleotides; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA