RG-7795

ANA773 is an oral Toll like-receptor 7 (TLR7) prodrug agonist whose active metabolite promotes natural killer (NK) cell-mediated anti-tumor response by inducing cytokine secretion, enhanced cytolysis of tumor cells by natural killer (NK cells) and enhanced antibody-dependent cellular cytotoxicity (ADCC). ANA773 induced the secretion of interferon-alpha (IFN-alpha) and various other cytokines from human peripheral blood mononuclear cells (PBMC) cultured in vitro. Innate immunity provides the first line of defense against tumor cells by inducing a broad immune response that includes the secretion of cytokines and the stimulation of NK cells. NK cells mediate anti-tumor activity by multiple mechanisms. NK cells directly lyse tumor cells through the secretion of cytotoxic granules; they promote apoptosis through the production of interferon-gamma (IFN-gamma), and they enhance the anti-tumor response of other immune cells. NK cells are activated by diverse signals, including type I interferons. Large amounts of type I IFN are produced by plasmacytoid dendritic cells (pDCs) upon engagement of the pattern recognition receptor TLR7. The natural ligand for TLR7 is single stranded RNA, although a variety of small molecule agonists have also been discovered. [Anadys Pharmaceuticals Press Release]