Figure 1.

TLR3 targeting by ARNAX for cancer immunotherapy.The chemical structure of ARNAX is shown to the upper left. MV: measeles virus. RNA essentially plays functions for life support in the nucleus and cytoplasm (left), but ARNAX does not affect these fundamental RNA functions. On the other hand, ARNAX taken up into cells induces signal response capable of activating IRF3 in myeloid cells (right). Although type I IFN and inflammatory cytokines are produced via the TICAM-1 pathway in this context, the serum cytokine levels are not significantly increased by ARNAX, unlike polyI:C. ARNAX reserves the ability to mature DC followed by immune cells activation, resulting in tumor repression (right). Molecular mechanism for capturing RNA in the membrane and transferring it to endosomes is not clear yet. MDA5 and RIG-I are cytoplasmic RNA sensors which cause robust cytokine production. TICAM-1 and MAVS are adapter molecules.