CpG oligodeoxynucleotides (ODNs) may prevent mortality from infection. We have identified a therapeutic benefit in treating sepsis with phosphorothioate ODN sequences containing the CpG motif. Sepsis was induced in rats by cecal ligation and puncture (CLP), and treatment with CpG ODNs reduced sepsis mortality from 80% to 15% during a 108-h period. Protection from mortality was dose dependent. B...

Synthetic phosphorothioate oligodeoxynucleotides (ODN) bearing unmethylated CpG motifs can mimic the immune-stimulatory effects of bacterial DNA and are recognized by Toll-like receptor 9 (TLR9). Past studies have demonstrated that nucleotide modifications at positions at or near the CpG dinucleotides can severely affect immune modulation. However, the effect of nucleotide modifications to stim...

CpG oligonucleotides (ODN) stimulate the innate immune system by triggering cells that express TLR9. The resulting response promotes tumor regression, an effect optimized by delivery of CpG ODN to the tumor site. This work examines the effect of instilling CpG ODN adsorbed onto polyketal microparticles (CpG-MP) into the lungs of mice with non-small cell lung cancer. Intrapulmonary delivery of C...

BACKGROUND Cytosine-phosphate-guanine (CpG) oligodeoxyribonucleotides (ODNs), which induce signaling via Toll-like receptor 9, have recently been suggested to enhance sensitivity to traditional therapies, including chemotherapy, in certain cancer cell lines. This study aimed to define the dose-effect relationship for CpG ODN 1826 in increasing radiosensitivity and its impact on immune function ...

Immunostimulatory CpG oligonucleotides (ODN) activate cells that express TLR9 and have been shown to improve the host's response to tumor Ags. Unfortunately, the immunosuppressive microenvironment that surrounds many cancers inhibits Ag-specific cellular responses and thus interferes with CpG-mediated immunotherapy. Myeloid-derived suppressor cells (MDSC) represent an important constituent of t...

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants in mice, boosting the humoral and cellular response to coadministered Ags. CpG ODN that stimulate human PBMC are only weakly active in mice. Thus, alternative animal models are needed to monitor the activity and safety of "human" CpG ODN in vivo. This work demonstrates that rhesus macaques recognize...

Phosphorothioate oligodeoxynucleotides containing CpG (CpG-ODN) activate immune responses. We report that quinacrine, chloroquine, and structurally related compounds completely inhibit the antiapoptotic effect of CpG-ODN on WEHI 231 murine B lymphoma cells and inhibit CpG-ODN-induced secretion of IL-6 by WEHI 231. They also inhibit IL-6 synthesis and thymidine uptake by human unfractionated PBM...

Different DNA motifs are required for optimal stimulation of mouse and human immune cells by CpG oligodeoxynucleotides (ODN). These species differences presumably reflect sequence differences in TLR9, the CpG DNA receptor. In this study, we show that this sequence specificity is restricted to phosphorothioate (PS)-modified ODN and is not observed when a natural phosphodiester backbone is used. ...

Numerous monoclonal antibodies (mAb) targeting tumor antigens have recently been developed. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) via effector cells such as tumor-infiltrating natural killer (NK) cells and macrophages are often involved in mediating the antitumor activity of mAb. CpG oligodeoxynucleotides (ODN) have a potent antitumo...

Accessibility of tumors for highly effective local treatment represents a major challenge for anticancer therapy. Immunostimulatory oligodeoxynucleotides (ODN) with CpG motifs are ligands of TLR9, which prime spontaneous antitumor immunity, but are less effective when applied systemically. We therefore developed a liposome-based agent for selective delivery of CpG-ODN into the tumor environment...