A new family of potent TLR9 agonists, EnanDIM, which inhibit tumor growth in various syngeneic murine models

Background: Toll-like receptor 9 (TLR9) agonists are DNA-based molecules known to be recognized by TLR9 via their non-methylated CG-motifs. They are developed as anti-cancer therapies due to their potential to broadly activate the innate and adaptive immune system. A new family of TLR9 agonists, EnanDIM® (Enantiomeric DNA-based Immunomodulator), consisting of linear single-stranded ODN with multiple CG motifs were developed. In contrast to other TLR9 agonists, protection against degradation by nucleases is achieved via L-deoxyribose nucleotides instead of the naturally occurring D-deoxyribose nucleotides at the 3’-ends. Thus, EnanDIM® molecules constitute a new family of TLR9 agonists avoiding chemical stabilization.