DDX nanoparticles-encapsulated IL-12 and RIG-I activating DNA plasmid EG-70

A nanoparticle-based formulation composed of a non-viral plasmid DNA vector encoding the human pro-inflammatory cytokine interleukin-12 (IL-12) and a retinoic acid-inducible gene I protein (RIG-I; DDX58) activating moiety encapsulated in dually derivatized chitosan (DDX) nanoparticles, with potential immunostimulating and antineoplastic activities. Upon intravesical administration of the DDX nanoparticles-encapsulated IL-12 and RIG-I activating DNA plasmid EG-70, the DDX nanoparticles deliver the IL-12 and RIG-I activating DNA plasmid to the bladder urothelium. This leads to local expression of IL-12 and a RIG-I activating moiety. The increased IL-12 production at the tumor site activates the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma (IFN-g) and promoting cytotoxic T-lymphocyte (CTL) responses against tumor cells. The RIG-I activating moiety activates the cytosolic RNA receptor RIG-I and induces RIG-I-mediated signaling. This upregulates interferon-alpha (IFN-a) and beta (IFN-b), and induces a potent IFN-mediated innate immune response against the tumor cells. This further induces the activation of NKs and CTLs and induces apoptosis in cancer cells.