Definition

An engineered fusion protein composed of the human pro-inflammatory cytokine interleukin-12 (IL-12) fused to a Fc domain and masked with protein domains, with potential immunomodulatory and antineoplastic activities. Upon administration of IL-12-Fc fusion protein KGX101, IL-12 is bound to the proteins and pharmacologically inactive. IL-12 does not become active until cleaved by tumor-specific matrix metalloproteinases in the tumor microenvironment (TME). Upon proteolytic cleavage, unbound and active IL-12 locally 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 Fc domain prolongs the half-life and exposure in the tumor.