Toll-like Receptor 9 Agonists Development
Creative Biolabs is a world leader in the field of cancer vaccine development. We provide quality Toll-like receptor 9 (TLR9) agonists development services for activating immune cells and their respective controls, with dedicated support from our experts in Creative Biolabs.
Several evidences suggest that early production of type I interferons, and induction of costimulatory molecule expression on dendritic cells, may be essential for the generation of durable and effective antitumor immunity. One way to accomplish this goal is through the induction of a Th1-like innate immune response, similar to what is generated in response to intracellular infections. The family of toll-like receptors (TLRs) appears to play a pivotal role in the generation of different classes of innate immune responses, by differential detection of conserved pathogen-expressed molecules. TLR3,7,8,9 are expressed within the endosomal compartments of some innate immune cells, where they appear to be “looking inward” to detect nucleic acid components of intracellular pathogens. Activation of these endosomal TLRs can induce strong Th1-like immune activation, with the secretion of type I IFN and strong CD8+ T cell responses. In particular, the targeting of TLR9 has emerged as a powerful tool in the generation of Th1 adaptive immunity and has shown promise for enhancing the efficacy of cancer vaccination.
Fig.1 TLR ligands and TLR signaling pathways. (Bing, 2016)
The Role of TLR9 as Receptor for CpG ODN
Toll-like receptor 9 (TLR9) senses unmethylated CpG dinucleotides, a hallmark of microbial DNA, that can be mimicked by synthetic oligonucleotides containing CpG motifs (CpG ODNs). TLR9 stimulation by CpG DNA or CpG ODNs triggers intracellular signaling leading to the activation of macrophages, dendritic cells (DC) and B cells, and the production of cytokines, chemokines, and immunoglobulins. Subsequently, cytokines produced by DC, such as IL-12, induce the differentiation of naive T cells into T helper 1 (Th1) and cytotoxic T-cells (CTL).
Toll-like Receptor 9 Agonists for Cancer Vaccines
Toll-like receptors (TLRs) have gradually emerged as potential targets of newer immunotherapies. Antitumor activity of CpG ODNs has also been established in numerous mouse models. Encouraging results in the treatment of cancers have come from phase I and II clinical trials using CpG ODNs as a tumor vaccine adjuvant, monotherapy, or in combination with chemotherapy. TLR-9 is preferentially expressed on endosome membranes of B-cells and plasmacytoid dendritic cells (pDC) and is known for its ability to stimulate specific immune reactions through the activation of inflammation-like innate responses. Several synthetic CpG oligonucleotides (ODNs) have been developed as TLR-9 agonists with the aim of enhancing cancer immune surveillance. In many preclinical models, CpG ODNs were found to suppress tumor growth and proliferation both in monotherapy and in addition to chemotherapies or target therapies.
Creative Biolabs is a leader in the field of vaccine development and has focused on the cancer vaccines for years. We have experienced experts and advanced platforms that are able to provide excellent services. If you are interested in our services, please contact us for more details.
Reference
- Bing, D.; et al. Targeting Toll-like receptors against cancer. Journal of Cancer Metastasis and Treatment. 2016, 2: 463-470.
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