Induction of tumor-specific immune responses by the TLR9 agonist EnanDIM in murine syngeneic tumor models

Background: Toll-like receptor 9 (TLR9) agonists bind via non-methylated CG-motifs to their molecular target TLR9. This results in an activation of innate and adaptive immunity. Preclinical and ongoing clinical studies support the application of TLR9 agonists for immunotherapy. EnanDIM® (Enantiomeric DNA-based ImmunoModulator) is a new family of TLR9 agonists consisting of linear single-stranded oligonucleotides. Protection against exonucleases is achieved by use of L-deoxyribose nucleotides instead of the omnipresent D-deoxyribose nucleotides at their 3'-ends. Activation of human peripheral blood mononuclear cells with EnanDIM-C results in pronounced secretion of cyto- and chemokines, like IFN-alpha and IP-10, as well as broad activation of immune cells, like monocytes, NK cells and dendritic cells. In mice, EnanDIM-C beneficially modulates the tumor microenvironment by increasing presence of CD8+ T cells. Since EnanDIM-C provides the necessary signals for the initiation of an immunological anti-tumor response, EnanDIM-C was evaluated in various syngeneic murine tumor models for its ability to induce specific anti-tumor responses and persistent immune memory.