title: CpG oligodeoxynucleotides with double stem-loops show strong immunostimulatory activity.
abstract: Based on the current understanding of TLR9 recognition of CpG ODN, we have tried to design a series of CpG ODNs that display double stem-loops when being analyzed for their secondary structures using 'mfold web server'. Proliferation of human PBMC and bioassay for IFN production were used as technical platforms in primary screening. Interestingly, two of them, designated as DSL01 and D-SL03, belonging to B class CpG ODN and C class CpG ODN respectively, showed vigorous immunostimulatory activity and were chosen for further tests. Flow cytometry analysis showed that both of them could activate human B cells, NK cells, mononuclear cells and T cells and up-regulate expression of CD80, CD86 and HLA-DR on the surface of subsets in human PBMCs. Furthermore, we demonstrated that those two ODNs potently stimulated proliferation of PBMC/splenocytes obtained from diverse vertebrate species. Noticeably, both of them displayed anti-breast cancer effect in mice when administered by peritumoral injection.
authors.affiliation: Department of Molecular Biology, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Wan
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.forename: Yongli
authors.initials: Y
authors.lastname: Yu
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017433:Protein Structure, Secondary; D011817:Rabbits; D051381:Rats; D013154:Spleen / Q000166:cytology; D013552:Swine; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma