Definition

A formulation consisting of lipid nanoparticle (LNP) encapsulating self-replicating RNA (srRNA) encoding human interleukin-12 (IL-12), with potential immunomodulatory and antineoplastic activities. Upon intratumoral injection of LNP encapsulated srRNA encoding human IL-12 JCXH-211, the LNPs bind to the plasma membrane of nearby tumor cells and release srRNA encoding IL-12 into the tumor cells. The srRNA amplifies within the tumor cells, and is translated by the cellular protein translation machinery to produce IL-12, which is secreted into the local tumor microenvironment (TME). The secretion of IL-12 activates the immune system by promoting the secretion of interferon-gamma (IFN-g), activating natural killer cells (NKs), and inducing cytotoxic T-lymphocyte (CTL) responses, which may enhance immune-mediated destruction of tumor cells and decrease tumor cell proliferation. In addition, the virus-based RNA replicon may trigger anti-viral innate immune responses, further killing tumor cells.