title: Accessing the therapeutic potential of immunostimulatory nucleic acids.
abstract: Short synthetic CpG oligodesoxynucleotides (CpG ODN) that activate plasmacytoid dendritic cells (PDC) and B-cells via the endosomal Toll-like receptor (TLR) 9 are the prototypical immunostimulatory nucleic acids (NAs), and their therapeutic potential is currently evaluated in numerous clinical trials. In recent years, NA recognition has emerged as a general means of virus detection by the innate immune system that involves at least seven receptors located in either the endosome or the cytosol. Endosomal TLRs are expressed selectively, and predominantly by immune cell types. By contrast, the expression of cytosolic NA receptors is ubiquitous, significantly widening the range of cell types that can be stimulated therapeutically by NAs to include even tumor cells. Here we discuss unique properties of each of these receptors, and argue that an understanding of the molecular basis of receptor-ligand interactions, and the development of chemically defined, selective ligands is required in order to fully realize the promise that NA immunetherapeutics hold.
authors.affiliation: Institute for Clinical Chemistry and Pharmacology, University Hospital, University of Bonn, Sigmund-Freud-Str. 25, Bonn, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.forename: Vera
authors.initials: V
authors.lastname: Wimmenauer
authors.forename: Martin
authors.initials: M
authors.lastname: Schlee
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D011070:Poly I-C / Q000276:immunology / Q000378:metabolism; D012313:RNA / Q000276:immunology* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D018168:Receptors, Retinoic Acid; D051193:Toll-Like Receptors; D012313:RNA; D004247:DNA; D053487:DEAD-box RNA Helicases; D011070:Poly I-C