protein-engineered interleukin-12 XTX301

An engineered form of the human cytokine interleukin-12 (IL-12) in which the IL-12 is conjugated, via a tumor protease-cleavable linker, to a protein-engineered masking domain that prevents the binding of IL-12 to its receptors while in circulation and a half-life extension domain that prolongs circulating half-life, with potential immunomodulatory and antineoplastic activities. Upon administration of protein-engineered IL-12 XTX301, IL-12 is bound to the masking domain and pharmacologically inactive. Upon proteolytic cleavage by matrix metalloproteinases (MMPs) 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.