Definition

An engineered, prodrug form of the human cytokine interleukin-12 (IL-12), composed of wild-type IL-12 linked to a high affinity blockade element via a tumor protease-sensitive linker, and a half-life extension domain, with potential immunomodulatory and antineoplastic activities. Upon administration of engineered IL-12 prodrug WTX-330, IL-12 is bound to the blockade element and pharmacologically inactive. Upon proteolytic cleavage in the tumor microenvironment (TME), active IL-12 is released. IL-12 activates the immune system by promoting the secretion of interferon-gamma (IFN-g) and activating CD8+ T-cells, CD4+ T cells and natural killer cells (NKs). The activation and expansion of these immune cells mediate cytolytic immune responses against tumor cells, thereby killing tumor cells and inhibiting tumor cell proliferation. The selective activation in the TME enhances the IL-12-mediated cytolytic responses against tumor cells while sparing the unwanted effects of systemic, peripheral immune activation. The inclusion of the half-life extension domain prolongs the agent’s exposure in the tumor.