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Synthetic Oligodeoxynucleotides Containing Deoxycytidyl-Deoxyguanosine Dinucleotides (CpG ODNs) and Modified Analogs as Novel Anticancer Therapeutics

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Abstract:

Oligodeoxynucleotides containing deoxycytidyl-deoxyguanosine dinucleotides (CpG ODNs) activate the host immune system, leading to innate and acquired immune responses. The immune stimulatory effects of CpG ODNs are being exploited as a novel therapeutic approach to treatment of human diseases, and some CpG ODNs are being evaluated in clinical trials. The cellular recognition of CpG motifs requires the presence of the Toll-like receptor (TLR) 9, which triggers cell signaling and immune responses. There are three main types of first-generation CpG ODNs, which mimic the immunostimulatory activity of bacterial DNA and are recognized by TLR9, A-, B- and C-Class ODNs. Although all three CpG ODN classes stimulate TLR9-dependent signaling, there are striking differences in the cell types they activate and their dose-dependent immunostimulatory efficacy. Second-generation CpG ODNs, with advanced nucleic acid chemistry and unique modifications to their sequences and structures are being developed. Medicinal chemistry studies suggest that the immunomodulatory activity of CpG ODNs can be altered by site-specific incorporation of modifications in order to develop disease-specific drugs. Both first- and second-generation CpG ODNs have potential for treatment of various human diseases, such as infections, immunodeficiencies, and cancers. This article will focus on the recent advances in developing CpG ODNs as novel anti-cancer therapeutic agents.

Keywords: cytokines; dendritic cells; immunogenicity; immunostimulatory; interferon; macrophages; natural killer (nk) cell; oligodeoxynucleotides; toll-like receptor; transduction pathways

Document Type: Review Article

DOI: https://doi.org/10.2174/1381612054546707

Affiliations: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, VH 113, Box 600, 1670 University Blvd., Birmingham, AL 35294-0019, USA.

Publication date: 2005-08-01

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    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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