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Immunotherapeutic applications of CpG-containing oligodeoxynucleotides
Date
2000-06-01
Author
Klinman, DM
Ishii, KJ
Gürsel, Mayda
Gursel, I
Takeshita, S
Takeshita, F
Metadata
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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
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Bacterial DNA and synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate the mammalian immune system to mount a rapid innate immune response. This response is characterized by the production of polyreactive IgM, immunomodulatory cytokines and chemokines. CpG ODN directly stimulate lymphocytes, natural killer cells and professional antigen-presenting cells (such as macrophages and dendritic cells). Owing to the strength and nature of this stimulation, CpG ODN are being harnessed for a variety of therapeutic uses. They are being tested for their ability to act as immune adjuvants, boosting the immune response elicited by conventional and DNA vaccines. As a result of their ability to activate a strong interferon gamma-dominated Th1 response while blocking the development of Th2-dependent allergies, CpG ODN are being examined for their antiallergic properties. Finally, CpG ODN are being used as "immunoprotective agents," since the innate immune response they elicit can protect the host from a variety of pathogenic bacteria, viruses and parasites. (C) 2000 Prous Science. All rights reserved.
Subject Keywords
Immunostimulatory Dna-Sequences
,
Natural-Killer Activity
,
B Surface-Antigen
,
Bacterial-Dna
,
Interferon-Gamma
,
Dendritic Cells
,
Cutting Edge
,
Murine Leishmaniasis
,
Immune-Responses
,
Phosphorothioate Oligodeoxynucleotides
URI
https://hdl.handle.net/11511/52830
Journal
DRUG NEWS & PERSPECTIVES
Collections
Department of Biology, Article
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Bacterial DNA and synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate the mammalian immune system to mount a rapid innate immune response. This response is characterized by the production of polyreactive IgM, immunomodulatory cytokines and chemokines. CpG ODN directly stimulate lymphocytes, natural killer cells and professional antigen-presenting cells (such as macrophages and dendritic cells). Owing to the strength and nature of this stimulation, CpG ODN are being harnessed f...
Immunotherapeutic utility of stimulatory and suppressive oligodeoxynucleotides.
Ishii, KJ; Gursel, I; Gürsel, Mayda; Klinman, DM (2004-04-01)
Bacterial DNA contains immunostimulatory CpG motifs that interact with toll-like receptor 9 on immune cells to stimulate the production of cytokines, chemokines and immunoglobulins. Synthetic oligodeoxynucleotides (ODNs) containing CpG motifs mimic the activity of bacterial DNA. Recently, several structurally distinct types of CpG ODN were identified that differentially activate human immune cells. These ODNs may be useful as vaccine adjuvants, anti-allergens and in the treatment of infectious diseases and ...
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Bacterial DNA and oligodeoxynucleotides containing immunostimulatory sequences with a CpG motif stimulated a Th1 type response in vivo. The adjuvant action of a non-coding plasmid DNA derived from pRc/CMV HBS (encoding the S region of hepatitis B surface antigen, HBsAg) in mice was investigated. The role of methylation on the adjuvanticity of the plasmid as well as the effect of vaccine formulation employed on the outcome of antigen-specific humoral and cellular responses were also studied. The results demo...
Immunomodulatory effects of commensal bacteria-derived membrane vesicles
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Constitutive secretion of extracellular membrane vesicles is a common feature of cells from all domains of life including Archaea, Bacteria, and Eukarya. Although the contribution of gram negative bacterial outer membrane vesicles in disease pathogenesis has been extensively studied, whether commensal bacteria constitutively secrete such vesicles is still unknown. Given the importance of microbiota as regulators of immune homeostasis, we aimed to assess the immunomodulatory properties of extracellular vesic...
Cutting edge: Role of toll-like receptor 9 in CpG DNA-induced activation of human cells
Takeshita, F; Leifer, CA; Gursel, I; Ishii, KJ; Takeshita, S; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2001-10-01)
Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines and PBMC that recognize CpG DNA express membrane-bound human Toll-like receptor 9 (hTLR9). Cells that are not responsive to CpG DNA become responsive when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake of CpG (but not control) DNA into endocytic vesicles. Upon cell stimulation, hTLR9 and CpG DNA are found in the same endocytic vesicles. Cells expressing hTLR9 are ...
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D. Klinman, K. Ishii, M. Gürsel, I. Gursel, S. Takeshita, and F. Takeshita, “Immunotherapeutic applications of CpG-containing oligodeoxynucleotides,”
DRUG NEWS & PERSPECTIVES
, pp. 289–296, 2000, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/52830.