TLR Immune Modulation

The innate immune response is the front line of defense against viruses, bacteria and other potential pathogens. Toll- Like Receptors (TLRs) are among the most important receptors used by all cell types to recognize and respond to the presence of these invaders. The human genome encodes 10 TLRs that are similar in structure, but recognize different parts of viruses or bacteria. Four of these TLRs recognize either DNA or RNA and are triggered by the genomes of microorganisms taken up by cells in specialized structures called endosomes.

The innate response sets the stage for the generation of an adaptive immune response composed of highly specific antibodies and T cells. By activating specific TLRs, it is possible to stimulate specific types of the innate immune response, leading to an enhanced adaptive response to vaccines, cancer-killing activities, or to modulation of allergic inflammation. Dynavax research has resulted in the identification of proprietary synthetic oligonucleotides (short segments of DNA), that selectively activate one of these important receptors, TLR9. These are called CpG oligonucleotides – CpGs for short – referring to the presence of specific nucleotide sequences containing the CG base pair.  In addition, Dynavax is developing compounds that activate two other important innate receptors, TLR7 and TLR8. This portfolio of novel and potent activators opens multiple opportunities for expanding the scope of cancer immunotherapy, enhancing the efficiency of vaccines and modulating allergic diseases.