The potential of CpG oligodeoxynucleotides in the development of dendritic cell vaccines

Abstract

Dendritic cells (DCs) are powerful antigen-presenting cells (APCs) capable of initiating a primary immune response, leading to the development of CD8 + cytotoxic T-cells (CTLs) and CD4 + T helper (Th) cells. These characteristics make them promising as vaccine carriers. However, despite the great potential demonstrated in murine models, DC-based vaccines have only been moderately effective in human clinical trials. The efficacy of DC-based vaccination or therapy depends on a number of variables, including antigen characteristics, DC lineage and level of maturation, vaccination route, frequency and interval, and host status. Many of these parameters need to be further optimized and/or understood before DC vaccines reach their full potential. Toll-like receptor (TLR) agonists are capable of activating DCs in response to pathogens and have potential as activation and maturation factors for DCs. The immunostimulatory properties of CpG oligodeoxynucleotides (ODNs), which signal through TLR9, have been extensively studied. The concept of using CpG ODNs stimulation of murine bone marrow-derived DCs (BM-DCs) has been proven mostly in tumor challenge models. According to several published reports, TLR9 is present on human plasmacytoid DCs and B-cells, but not on monocytes, which are the most common source of DC vaccines. However, a recent study demonstrated expression of TLR9 on human monocyte-derived DCs, which suggests that CpG ODNs might be useful as activation and maturation factors. Furthermore, TLR7 and TLR8 activation was found to have a similar mode of action to TLR9. TLR8 is expressed on human monocytes and monocyte-derived DCs, and TLR8 agonists may therefore also have potential in the generation of DC vaccines.